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Palmoplantar pustulosis (PPP) is a chronic inflammatory skin disease characterized by recurrent pustules on the palms and soles. Current treatments, including topical medications, phototherapy, and systemic therapies, often show limited efficacy. Upadacitinib (UPA), a selective JAK1 inhibitor, has shown potential in treating neutrophilic dermatoses by modulating cytokine activity. To evaluate the efficacy and safety of UPA compared with acitretin (ACI) in the acute phase of PPP through a prospective cohort study. This study was conducted at the Shanghai Skin Disease Hospital from August 2024 to January 2025. A total of 79 patients with acute PPP were enrolled and randomly assigned to receive UPA (15 mg daily) or ACI (20 mg daily) for 4 weeks. Efficacy was assessed using pustule counts, Palmoplantar Pustulosis Area and Severity Index (PPPASI), and Dermatology Life Quality Index (DLQI). Safety was evaluated by recording adverse events (AEs). At week 2, the rate of complete pustule clearance was significantly higher in the UPA group (41.9%) than in the ACI group (10.5%, P = 0.003). By week 4, all patients in the UPA group achieved a pustule count < 30, compared with 63.2% in the ACI group. The UPA group also showed greater reductions in PPPASI and higher response rates for PPPASI 50/75/90. Quality of life improvements, as measured by DLQI, were more pronounced in the UPA group. In terms of safety, UPA had a favorable profile with lower overall AE incidence compared with ACI. UPA demonstrated superior efficacy over ACI in rapidly clearing pustules and improving skin lesions and quality of life in acute PPP episodes. The findings suggest that JAK1 inhibition may be a promising therapeutic approach for PPP, warranting further investigation in larger trials. [ www.chictr.org.cn ], identifier [ChiCTR2000036186].

Pelvic exenteration (PE) entails an&#xa0;en bloc resection of locally advanced primary or recurrent rectal cancer. This study aimed to assess&#xa0;the short-term and survival outcomes of minimally invasive (MI)- and open PE. A&#xa0;retrospective cohort analysis of patients with stage III rectal adenocarcinoma treated with PE from the National Cancer Database (2010-2019)&#xa0;was conducted. Open and MI-PE were matched for baseline and treatment characteristics using 2:1 propensity score matching. Primary outcomes were 30- and 90-day mortality; secondary outcomes included 30-day readmission, hospital stay, surgical margins, lymph node yield, and overall survival (OS). PE was performed in 1010 (1.9%) of 52,242 patients; 705 (69.8%) were open and 304 were (30.2%) MI procedures. After matching, 169 patients in the MI-PE group were matched to 338 patients in the open PE group. The matched cohort included 507 patients (54.2% female). Hospital stay was shorter after MI compared to open PE (median: 6 vs. 8 days, p&#x2009;<&#x2009;0.001). MI and open PE had similar odds of 30- (OR: 0.33, p&#x2009;=&#x2009;0.306) and 90-day mortality (OR: 0.29, p&#x2009;=&#x2009;0.113), and comparable rates of positive surgical margins (12.7% vs. 15%, p&#x2009;=&#x2009;0.586) and suboptimal lymph node yield (19% vs. 26%, p&#x2009;=&#x2009;0.096). MI-PE had a similar OS to open surgery (82.5 vs. 77.5 months, p&#x2009;=&#x2009;0.281). Robotic-assisted PE was associated with significantly lower odds of conversion to open surgery (OR: 0.15, p&#x2009;=&#x2009;0.003) and shorter hospital stay (median: 5 vs. 7 days, p&#x2009;=&#x2009;0.026) than laparoscopic PE. MI-PE provided similar pathologic and survival outcomes to open PE with comparable short-term mortality rates and significantly shorter hospital stays.

Local injection of a small amount of blue dye into the submucosa can facilitate recognizing the dissection line in endoscopic submucosal dissection (ESD). Amber-red color imaging (ACI), which hardly affects the submucosal blue color, is suitable for the entire ESD. This study aimed to clarify characteristics of ACI during ESD. Nine endoscopic images were selected during submucosal dissection in four cases of gastric ESD to evaluate endoscopic ACI and white light imaging (WLI). Visibility of the dissection line and the submucosal vessel were evaluated by eight endoscopists using a 5-point Likert scale. The blue submucosal area of each endoscopic image and color signal surrounding the submucosa were compared between ACI and WLI. In addition, the color signals in gradient dilutions of blue solutions were compared in ex vivo experiments. Visibility of the dissection line was better in ACI than in WLI and visibility of the submucosal vessels was slightly better in ACI. The size ratio of the blue area in ACI and WLI (i.e., ACI/WLI) ranged from 0.53 to 0.65, indicating that the blue area in the ACI was narrower. The red signal intensity of the surroundings with respect to the submucosa was greater in ACI than in WLI, which was related to the narrower blue area in ACI. Ex vivo experiments corroborated this observation. ACI highlights the submucosa in blue only where sufficient solution is injected, which facilitates recognition of the dissection line during ESD.

High-efficiency inverted (p-i-n) wide-bandgap (WBG &#x2265; 1.67 eV) perovskite solar cells (PSCs) are essential for tandem photovoltaics but remain constrained by surface defects and interfacial recombination at the perovskite/electron transport layer (ETL) interface. This study introduces an interfacial engineering approach involving the formation of a phase-pure quasi-2D perovskite layer (n = 2; PEA2FAPb2X7, X = I/Br) atop a WBG perovskite (1.67 eV). By optimizing the 2D precursor concentration, we enable a templated epitaxial-like growth of low-dimensional perovskite along the (110) plane of the 3D perovskite absorber layer, enhancing interfacial electronic coupling and defect passivation. Density functional theory (DFT) calculations reveal that phenylethylammonium (PEA+) cations preferentially adsorb at Pb2+ and I- vacancies, effectively passivating surface defects, suppressing nonradiative recombination, and improving interfacial band alignment. This interfacial modification results in a 100 mV increase in open-circuit voltage (VOC) and 17% improvement in power conversion efficiency (PCE). The optimized 3D/2D PSCs demonstrate a champion PCE of 21.22% (0.06 cm2), 20.58% (0.175 cm2), and 18.72% (0.805 cm2), and an improved VOC of 1.23 V. Additionally, unencapsulated devices retain over 80% of their initial PCE after 4000 h of storage in N2 environment, along with excellent thermal and photostability. These findings underscore the potential of templated quasi-2D perovskite interlayers in improving both the efficiency and long-term stability of WBG perovskite top cells for tandem photovoltaics.

Third-generation autologous chondrocyte implantation (ACI), also known as matrix-induced ACI (MACI), was approved for clinical practice in December 2016. Studies specifically investigating outcomes of MACI for complex patellofemoral chondral lesions are limited. To report patient-reported outcome measures (PROMs), complications, and failure rates after MACI for patellofemoral chondral defects at a minimum follow-up of 2 years. Case series; Level of evidence, 4. For this retrospective review of prospectively collected data, the authors identified patients who underwent treatment with MACI for focal chondral defects in the knee between August 2017 and September 2020. PROMs, including International Knee Documentation Committee (IKDC) score, Kujala score for patellofemoral disorders, and the Veterans RAND 12-item Health Survey (VR-12) score, were obtained preoperatively and a minimum of 2 years postoperatively. The percentage of patients who met the minimal clinically important difference (MCID) for each PROM was reported. Failure was defined as (1) graft failure on follow-up magnetic resonance imaging or second-look arthroscopy, (2) revision MACI or other chondral procedure, or (3) conversion to unicompartmental or total knee arthroplasty. A total of 50 patients (34 female; mean age, 32.43 &#xb1; 7.33 years; mean follow-up, 2.71 &#xb1; 0.79 years) remained after application of the exclusion criteria. There was a significant increase in all PROMs from preoperatively to postoperatively, including the IKDC (43.39 vs 68.58; P < .001), Kujala (58.93 vs 77.07; P < .001), VR-12 Mental (53.12 vs 57.90; P = .002), and VR-12 Physical (40.40 vs 49.89; P < .001) scores, with 5 (10%) failures. The MCID was achieved by 77.8% of patients in IKDC score and 69.0% in the Kujala score. Kaplan-Meier survival analysis showed survival probabilities of 98.0%, 96.0%, and 85.7% at 1, 2, and 4 years, respectively. MACI for patellofemoral bipolar lesions (n = 11) showed significant improvement in IKDC (50.06 vs 74.07; P = .008) and Kujala (69.33 vs 84.33; P = .046) scores, and 2 (18.2%) failures. Kaplan-Meier survival analysis with log-rank test demonstrated no significant differences in survival distributions between unipolar and bipolar patellofemoral lesions (P = .387). Third-generation ACI (MACI) is a successful and effective treatment method for difficult-to-treat patellar, trochlear, and bipolar patellofemoral chondral defects.

Bowel preparation is essential for colonoscopy but may deter patients. Although low volume laxatives are better tolerated, their impact on patient-reported outcomes remains unclear. We compared low and intermediate volume bowel preparation and assessed their impact on tolerability, health-related quality of life (HRQoL), and work. We conducted an open-label, noninferiority randomized trial in four Dutch hospitals. Patients were randomized to 2 L polyethylene glycol with ascorbate (2L PEG+Asc) or 1 L with added sodium sulfate (1L PEG+Asc). Before and after preparation, patients completed validated questionnaires on productivity, tolerability, and HRQoL. The primary outcome was the proportion of patients with adequate bowel preparation, aiming to demonstrate noninferiority of 1L PEG+Asc vs. 2L PEG+Asc (5% noninferiority margin). Secondary outcomes included willingness to repeat, with exploratory analysis of associated factors using multivariable logistic regression, change in HRQoL scores, tolerability, and work-related impact. We included 467 patients (2L PEG+Asc, n = 229; 1L PEG+Asc, n = 238). 1L PEG+Asc was noninferior to 2L: adequate cleansing rate, 96.1% (95%CI 92.6% to 98.0%) vs. 96.4% (95%CI 93.0% to 98.3%; P = 0.84; &#x394; &#x2212;0.4, 95%CI &#x2212;4.0 to 3.3). More patients in the 1L PEG+Asc group were willing to repeat the preparation (59.9% vs. 48.3%; P = 0.04), with tolerability the most influential factor (odds ratios 0.05 and 0.22 for difficult or fair vs. good tolerability, adjusted for symptoms, satisfaction, and 1L/2L PEG+Asc). No clinically relevant changes in HRQoL were observed. Absenteeism and impaired work productivity occurred in 7.9% and 12.3%, respectively, with no between-group differences. Bowel preparation with 1L PEG+Asc is noninferior to 2L PEG+Asc and associated with higher willingness to repeat. Tolerability is fundamental for effective cleansing and reducing colonoscopy barriers.

Current guidelines recommend selective adjuvant chemotherapy for stage II colon cancer with high-risk features. This study aimed to assess survival benefit of adjuvant chemotherapy in patients with stage II colon adenocarcinomas &#x2265;5&#xa0;cm without high-risk features. The National Cancer Database was retrospectively reviewed (2010-2019) for all patients with pathologic stage II colonic adenocarcinomas &#x2265;5&#xa0;cm who underwent colectomy. Patients were divided into adjuvant and control groups that were propensity-score matched for baseline and treatment confounders. The primary outcome was 5-year overall survival (OS). Of 23,937 included patients, adjuvant chemotherapy was given to 2581 (10.8&#xa0;%). Patient given adjuvant chemotherapy were younger, more often male, Black, had a Charlson score of 0 and private insurance, presented with left-sided cancers and microsatellite stable (MSS) tumors, and more frequently underwent segmental resections and open surgery. 796 patients in the adjuvant group were matched to 1592 patients in the control group. Adjuvant chemotherapy was associated with lower mortality (HR: 0.79; p&#xa0;=&#xa0;0.022), however, it was not independently associated with improved OS when adjusted for other confounders (HR: 0.84; p&#xa0;=&#xa0;0.157). The adjuvant group had significantly longer restricted mean OS than the control group (104.9 vs. 100.8 months; p&#xa0;=&#xa0;0.007). The survival benefit was only noted in patients >50 years, female, White, with non-mucinous adenocarcinomas, MSS tumors, normal CEA levels, and had undergone open and emergency surgery. The study did not demonstrate a clear survival benefit from adjuvant chemotherapy in patients with stage II adenocarcinoma &#x2265;5&#xa0;cm. A possible potential survival benefit was observed only in a subgroup of patients.

Well-designed mobile health (mHealth) applications can improve patient outcomes; however few clinically tested apps are developed with user-centric design. ASTHMAXcelED is a patient-facing mobile application designed for emergency department (ED) asthma patients. We studied user acceptance of the application and compared asthma control and quality of life measures before and after use of ASTHMAXcelED. This prospective cohort study was conducted in two large urban EDs. Inclusion criteria were patients &#x2265;18 years, English literacy, smartphone access, and discharge from the ED diagnosed with asthma exacerbation. ASTHMAXcelED was downloaded onto participants' phones upon discharge. Asthma symptom control was measured using the Asthma Control Test (ACT). User acceptance of and intention to use the application after the study period was measured using a Unified Theory of Acceptance and Use of Technology. A total of 149 participants were enrolled in the study, of which 124 completed follow-up visits. The proportion of patients with good asthma control (ACT&#x2009;>&#x2009;19) improved from 27% at baseline to 54% at 4-week follow-up, p &#x2009;<&#x2009;0.01. The rate of ED revisit was 7% and hospitalization for asthma was 0%. A total of 39% of patients indicated they intended to continue using ASTHMAXcelED in the next 6 months, whereas 5% did not. While using ASTHMAXcelED for 4 weeks, participant's asthma symptom control and quality of life scores improved. Their ED revisit rate and asthma hospitalization during the study period were low. ASTHMAXcelED may be an easily adopted mhealth education platform that can improve patient outcomes.

There is limited research on how emergency investments can support national health information system strengthening both for a given health emergency response and for routine health program areas. This study examined the effect of COVID-19 vaccine digital investments on advancing national digital health system architectures in Burkina Faso, Indonesia, Mali and Suriname. Primary qualitative data were collected through purposively sampled key informant interviews and focus group discussions with 67 key stakeholders from government institutions, donors and implementing partners from February to May 2023. Primary data were triangulated with secondary data collected through desk review and were analyzed deductively and inductively using thematic coding. The study found that although USAID's COVID-19 vaccine digital investments in Burkina Faso, Indonesia, Mali and Suriname did not contribute to the development of formal national digital health architecture documentation, progress was made in strengthening components of national digital health architectures, specifically around standards and interoperability and around governance. Progress was also made in motivating government stakeholders to invest in formal digital health transformation efforts. Lessons learned from this study suggest that connecting investments in system development and enhancement with investments in governance and infrastructure can improve country data management processes and data use for decision-making in routine health and emergency responses. Abr&#xe9;g&#xe9; Peu de recherches ont &#xe9;t&#xe9; effectu&#xe9;es sur la fa&#xe7;on dont les investissements fournis dans les situations d'urgence peuvent appuyer le renforcement du syst&#xe8;me national d'information sur la sant&#xe9;, tant pour une intervention d'urgence sanitaire donn&#xe9;e que pour les secteurs de programmes de sant&#xe9; courants. Cette &#xe9;tude examine l'effet des investissements num&#xe9;riques dans le vaccin contre la COVID-19 sur le d&#xe9;veloppement des architectures nationales des syst&#xe8;mes de sant&#xe9; num&#xe9;riques au Burkina Faso, en Indon&#xe9;sie, au Mali et au Suriname. Les donn&#xe9;es qualitatives primaires ont &#xe9;t&#xe9; recueillies au moyen d'entretiens aupr&#xe8;s d'informateurs cl&#xe9;s &#xe9;chantillonn&#xe9;s de mani&#xe8;re cibl&#xe9;e et de discussions de groupes avec 67 parties prenantes cl&#xe9;s issues d'organismes gouvernementaux, de donateurs et de partenaires de mise en &#x153;uvre entre les mois de F&#xe9;vrier et Mai 2023. Les donn&#xe9;es primaires ont &#xe9;t&#xe9; triangul&#xe9;es avec les donn&#xe9;es secondaires recueillies par le biais d'une &#xe9;tude documentaire et ont &#xe9;t&#xe9; analys&#xe9;es de mani&#xe8;re d&#xe9;ductive et inductive &#xe0; l'aide d'un codage th&#xe9;matique. L'&#xe9;tude a r&#xe9;v&#xe9;l&#xe9; que, bien que les investissements num&#xe9;riques de l'USAID en faveur du vaccin contre la COVID-19 r&#xe9;alis&#xe9;s au Burkina Faso, en Indon&#xe9;sie, au Mali et au Suriname n'aient pas contribu&#xe9; au d&#xe9;veloppement d'une documentation officielle sur l'architecture num&#xe9;rique de la sant&#xe9;, des progr&#xe8;s ont &#xe9;t&#xe9; r&#xe9;alis&#xe9;s dans le renforcement de certains &#xe9;l&#xe9;ments des architectures num&#xe9;riques nationales de la sant&#xe9;, en particulier autour des normes et de l'interop&#xe9;rabilit&#xe9; et autour de la gouvernance. Des progr&#xe8;s ont &#xe9;galement &#xe9;t&#xe9; r&#xe9;alis&#xe9;s s'agissant d'inciter les acteurs gouvernementaux &#xe0; investir dans les efforts formels de transformation de la sant&#xe9; num&#xe9;rique. Les enseignements tir&#xe9;s de cette &#xe9;tude montrent que lier les investissements dans le d&#xe9;veloppement et l'am&#xe9;lioration des syst&#xe8;mes aux investissements dans la gouvernance et les infrastructures permet d'am&#xe9;liorer les processus de gestion des donn&#xe9;es nationales et l'utilisation des donn&#xe9;es pour la prise de d&#xe9;cisions dans les interventions sanitaires d'urgence et de routine. Resumen Son limitadas las investigaciones sobre la manera en que las inversiones de emergencia pueden apoyar el fortalecimiento de los sistemas nacionales de informaci&#xf3;n de salud, tanto para la respuesta a una emergencia sanitaria determinada como para &#xe1;reas de programas de salud de rutina. En este estudio se examin&#xf3; el efecto de las inversiones digitales en vacunas contra la COVID-19 sobre el avance de las estructuras de los sistemas nacionales de salud digital en Burkina Faso, Indonesia, Mal&#xed; y Surinam. Se recopilaron datos cualitativos primarios a trav&#xe9;s de entrevistas con informantes clave muestreadas intencionalmente y discusiones de grupos focales con 67 interesados clave de instituciones gubernamentales, donantes y socios implementadores de Febrero a Mayo de 2023. Los datos primarios se triangularon con datos secundarios recopilados mediante revisi&#xf3;n documental y se analizaron de forma deductiva e inductiva mediante codificaci&#xf3;n tem&#xe1;tica. En el estudio se hall&#xf3; que, aunque las inversiones digitales de USAID en vacunas contra la COVID-19 en Burkina Faso, Indonesia, Mal&#xed; y Surinam no contribuyeron al desarrollo de la documentaci&#xf3;n formal de las estructuras nacionales de salud digital, s&#xed; ayudaron a fortalecer ciertos componentes de esas estructuras, espec&#xed;ficamente en relaci&#xf3;n con las normas y la interoperabilidad y con la gobernanza. Tambi&#xe9;n se avanz&#xf3; en la motivaci&#xf3;n de las partes interesadas gubernamentales para que inviertan en esfuerzos formales de transformaci&#xf3;n de la salud digital. Las lecciones aprendidas a partir de este estudio sugieren que conectar las inversiones en el desarrollo y la mejora del sistema con las inversiones en gobernanza e infraestructura puede mejorar los procesos de gesti&#xf3;n de datos nacionales y el uso de datos para la toma de decisiones en las respuestas de rutina de salud y emergencia.

This study was to investigate the correlation between serum calprotectin (Cal) and the severity and outcome of patients with acute cerebral infarction (ACI). Clinical data and serum Cal data were collected from 160 ACI patients and 60 healthy individuals. ACI patients were grouped according to their prognosis. Clinical data, biochemical indicators, and Cal levels were measured. Correlations between serum Cal and National Institute of Health stroke scale (NIHSS) scores, Glasgow Coma Scale (GCS) scores, and hematocrit (HCT) were analyzed. In ACI patients, elevated serum Cal levels were observed. These levels were positively correlated with NIHSS scores and inversely correlated with GCS scores and HCT. The receiver operating characteristic curve showed that serum Cal had an area under the curve of 0.770 for predicting poor outcomes, with a diagnostic cutoff of 18.01&#x2009;mg/L. Serum Cal levels over 18.01&#x2009;mg/L were independently related to poor prognosis for ACI and were identified as an independent risk factor for adverse outcomes. Serum Cal shows high expression in patients with ACI. Serum Cal has a good predictive value for the outcome of ACI.

Membrane autologous chondrocyte implantation (m-ACI) has become an increasingly applied and effective method for treating cartilage defects. Traditional open m-ACI procedures prolong patient recovery time and increase the risks of trauma and knee stiffness. With the application of fibrin glue and improvements in surgical skills, the procedure has evolved from traditional open surgery to an all-arthroscopic technique. This transition has made m-ACI a minimally invasive, cosmetically favorable surgical procedure, which facilitates faster recovery and is increasingly promoted.

Eimeria necatrix, a member of the Apicomplexa phylum, is one of the most pathogenic parasites, causing high mortality in chickens. Microneme proteins (MICs) play essential roles in host cell recognition and invasion by apicomplexan parasites and are also attractive candidates for vaccine development. However, comprehensive studies on E. necatrix MICs remain limited. Eimeria necatrix MIC3 gene (EnMIC3) was amplified and expressed in Escherichia coli. The recombinant protein (rEnMIC3) was characterized via SDS-PAGE and Western blot. The antigenicity of rEnMIC3 and its localization in sporozoites (SZ) and second-generation merozoites (MZ-2) of E. necatrix were determined by Western blot and indirect immunofluorescence analyses (IFAs). The dynamic expression of EnMIC3 across different developmental stages and its impact on sporozoite invasion of host cells were analyzed. The immune protection provided by rEnMIC3 was evaluated in chickens using weight gain, lesion scores, oocyst production, anticoccidial index (ACI), and antibody levels. The open reading frame of EnMIC3 was 798&#xa0;bp, encoding a 265-amino acid protein with a predicted molecular weight of 28.50&#xa0;kDa. EnMIC3 contained a signal peptide and a single epidermal growth factor (EGF)-like domain. The rEnMIC3 with an approximate molecular weight of 36&#xa0;kDa could be specifically recognized by convalescent sera from chickens infected with E. necatrix. The molecular mass of the native protein was approximately 35&#xa0;kDa, and it localizes to the apical region in SZ but exhibits a cytoplasmic distribution in MZ-2. EnMIC3 mRNA was expressed at significantly higher levels in SZ than in MZ-2, whereas protein expression displayed an inverse pattern. Anti-rEnMIC3 polyclonal antibodies inhibited sporozoite invasion of DF-1 cells in a dose-dependent manner. Vaccination with rEnMIC3 conferred effective protection against E. necatrix challenge, with the high-dose group (200&#xa0;&#xb5;g) achieving the highest ACI value (171.32) and markedly elevated serum antibody levels. These findings not only offer a foundation for understanding the role of EnMIC3 protein in the host invasion of E. necatrix but also present a potential protective antigen of E. necatrix for the development of a subunit vaccine against avian coccidiosis.

This study aimed to assess the efficacy of a biomedical informatics boot camp with regard to improving the skill sets of its participants.The University at Buffalo hosts a free, virtual biomedical informatics boot camp annually. Lectures covering various subject matters are offered, for example, general programming, machine learning, natural language processing, and clinical decision support. Once the 2023 boot camp had concluded, an anonymous voluntary survey was distributed.Seventy percent of the survey respondents indicated that they agreed that their expectations were met. Eighty-two percent of the respondents indicated that our JupyterHub and the associated educational coding materials are useful tools for learning. Free response answers showed a desire for additional hands-on courses over theoretical lectures.The results were overwhelmingly positive. Most respondents felt they had expanded upon their knowledge of informatics. The study also pointed out challenges, including keeping difficulty levels appropriate for an audience with diverse educational backgrounds.

Digital health global goods software are accessible, adaptable and scalable tools that can contribute to strengthened health data management and service delivery. This study explored how government stakeholders in three countries (Burkina Faso, Mali and Suriname) selected digital health global goods for COVID-19 vaccine response efforts, including whether and how these digital tools were adapted and scaled, challenges that were encountered and lessons learned from the experience. Primary data were collected through 28 purposively sampled, semi-structured key informant interviews between March and May 2023 with national- and regional-level stakeholders involved in COVID-19 vaccination response efforts. Qualitative data were analyzed deductively and inductively using thematic coding. Ministries of health in each country selected District Health Information Software 2 (DHIS2) as a COVID-19 vaccine tracking information system, but the system selection and configuration process differed. Key factors that most influenced the use of DHIS2 included country familiarity with the tool, urgent demand for real-time data and partner influence. Supportive supervision and reinforcement of data quality contributed to the effective use of DHIS2. Contextual factors, including adequate infrastructure and funding, posed challenges in system use. Experience using DHIS2 during the COVID-19 pandemic has led to plans for its expanded use in other health areas. Based on the findings, the authors recommend ministries of health utilize familiar global goods systems during health emergency periods, donors coordinate to streamline future digital system investments and technical and financial partners support countries to invest in the enabling environment for global goods systems to effectively and sustainably operate. Abr&#xe9;g&#xe9; Les logiciels de produits mondiaux de sant&#xe9; num&#xe9;rique sont des outils accessibles, adaptables et &#xe9;volutifs qui peuvent contribuer &#xe0; renforcer la gestion des donn&#xe9;es de sant&#xe9; et la prestation des services. Cette &#xe9;tude a examin&#xe9; la fa&#xe7;on dont les parties prenantes publiques de trois pays (Burkina&#xa0;Faso, Mali et Suriname) ont s&#xe9;lectionn&#xe9; des produits mondiaux de sant&#xe9; num&#xe9;rique pour des campagnes vaccinales contre la COVID-19, y compris si et en quoi ces outils num&#xe9;riques ont &#xe9;t&#xe9; adapt&#xe9;s et mis &#xe0; l'&#xe9;chelle, les probl&#xe8;mes rencontr&#xe9;s et les enseignements tir&#xe9;s de l'exp&#xe9;rience. Les donn&#xe9;es primaires ont &#xe9;t&#xe9; recueillies par le biais de 28&#xa0;entretiens semi-structur&#xe9;s aupr&#xe8;s d'informateurs&#xa0;cl&#xe9;s &#xe9;chantillonn&#xe9;s de mani&#xe8;re cibl&#xe9;e entre les mois de mars et mai&#xa0;2023 avec des parties prenantes nationales et r&#xe9;gionales associ&#xe9;es aux campagnes vaccinales contre la COVID-19. Les donn&#xe9;es qualitatives ont &#xe9;t&#xe9; analys&#xe9;es de mani&#xe8;re d&#xe9;ductive et inductive &#xe0; l'aide d'un codage th&#xe9;matique. Les minist&#xe8;res de la Sant&#xe9; de chacun des pays ont choisi District&#xa0;Health information Software&#xa0;2 (DHIS2) comme syst&#xe8;me informatis&#xe9; de suivi de la vaccination contre la COVID-19, mais le processus de s&#xe9;lection et de configuration du syst&#xe8;me &#xe9;tait diff&#xe9;rent. Les principaux facteurs qui ont le plus influ&#xe9; sur l'utilisation de DHIS2 &#xe9;taient&#xa0;: la familiarit&#xe9; des pays avec l'outil, la demande urgente de donn&#xe9;es en temps r&#xe9;el et l'influence des partenaires. La supervision, le soutien et le renforcement de la qualit&#xe9; des donn&#xe9;es ont contribu&#xe9; &#xe0; l'utilisation efficace de DHIS2. Des facteurs contextuels, y compris une infrastructure et un financement adapt&#xe9;s, ont pr&#xe9;sent&#xe9; des difficult&#xe9;s dans l'utilisation du syst&#xe8;me. L'exp&#xe9;rience de l'utilisation de DHIS2 pendant la pand&#xe9;mie de COVID-19 a conduit &#xe0; des projets d'extension de son utilisation dans d'autres domaines de la sant&#xe9;. Sur la base des r&#xe9;sultats obtenus, les auteurs recommandent que pendant les p&#xe9;riodes d'urgence sanitaire, les minist&#xe8;res de la Sant&#xe9; utilisent des syst&#xe8;mes de produits mondiaux connus, que les donateurs coordonnent leurs efforts pour rationaliser les futurs investissements dans les syst&#xe8;mes num&#xe9;riques et que les partenaires techniques et financiers aident les pays &#xe0; investir dans un environnement propice au fonctionnement efficace et durable des syst&#xe8;mes de produits mondiaux. Resumen Los programas inform&#xe1;ticos de bienes globales digitales para la salud son herramientas accesibles, adaptables y ampliables que pueden contribuir a reforzar la gesti&#xf3;n de los datos sanitarios y la prestaci&#xf3;n de servicios. En este estudio se examina c&#xf3;mo las partes interesadas gubernamentales de tres pa&#xed;ses (Burkina Faso, Mal&#xed; y Surinam) seleccionaron bienes globales digitales de salud para los esfuerzos de vacunaci&#xf3;n en respuesta a la COVID-19, incluyendo si y c&#xf3;mo estas herramientas digitales fueron adaptadas y ampliadas, los desaf&#xed;os que se hallaron y las lecciones aprendidas de la experiencia. Los datos primarios se recopilaron a trav&#xe9;s de 28 entrevistas semiestructuradas a informantes clave con muestreo intencional. Las entrevistas se realizaron entre marzo y mayo de 2023 con partes interesadas a nivel nacional y regional implicadas en los esfuerzos de vacunaci&#xf3;n contra la COVID-19. Los datos cualitativos se analizaron de forma deductiva e inductiva mediante codificaci&#xf3;n tem&#xe1;tica. Los ministerios de Salud de cada pa&#xed;s seleccionaron el District Health Information Software 2 (DHIS2) como sistema de informaci&#xf3;n para el seguimiento de las vacunas contra la COVID-19, pero el proceso de selecci&#xf3;n y configuraci&#xf3;n del sistema fue diferente. Los factores clave que m&#xe1;s influyeron en el uso de DHIS2 fueron la familiaridad del pa&#xed;s con la herramienta, la demanda urgente de datos en tiempo real y la influencia de los socios. La supervisi&#xf3;n de apoyo y el refuerzo de la calidad de los datos contribuyeron al uso eficaz de DHIS2. Ciertos factores contextuales, como la infraestructura y la disponibilidad de fondos, plantearon retos en el uso del sistema. La experiencia en el uso de DHIS2 durante la pandemia de COVID-19 ha dado lugar a planes para ampliar su uso en otros &#xe1;mbitos sanitarios. Bas&#xe1;ndose en los hallazgos, los autores recomiendan a los ministerios de Salud que utilicen sistemas conocidos de bienes globales durante los per&#xed;odos de emergencia sanitaria; a los donantes, que se coordinen para racionalizar las futuras inversiones en sistemas digitales, y a los socios t&#xe9;cnicos y financieros, que apoyen a los pa&#xed;ses para que inviertan en un entorno propicio en que los sistemas de bienes globales puedan funcionar de manera eficaz y sostenible.

The zonal organization of articular cartilage is critical for the biphasic mechanical properties of the tissue. Current treatments for articular cartilage have yet to regenerate this zonal architecture, compromising the functional efficacy of the repaired tissue, which could account for tissue failure in the long term. Autologous chondrocyte implantation (ACI) still suffers from inconsistent efficacy and a long recovery period stemming from implantation of a heterogeneous chondrocyte mixture. Stratified implantation of zonal chondrocytes would facilitate the recapitulation of articular cartilage zonal properties and improve the repair efficacy of ACI treatment. Controlled laboratory study. Autologous chondrocytes extracted from porcine articular cartilage were subjected to dynamic microcarrier expansion followed by size-based segregation using a spiral microfluidic device for the enrichment of zonal chondrocytes. Zonal chondrocytes were implanted into a chondral defect as a bilayered hydrogel construct consisting of superficial zone chondrocytes overlaying middle/deep zone chondrocytes (n = 6). Twelve months after implantation, the repair efficacy was compared against implantation of full-thickness cartilage-derived heterogeneous chondrocytes expanded on tissue culture plates (n = 5) or microcarriers (n = 6). Quantitative assessment of the repair tissues, including gross morphology, histological analysis, micro-computed tomography (micro-CT), compression modulus, and surface lubrication analysis, at 12 months demonstrated statistically significant improvement in cartilage and subchondral bone repair with zonal chondrocyte bilayered implantation. Magnetic resonance imaging (MRI) T2 mapping indicated progressive improvement in graft maturation as early as 3 months, reaching normalcy at 9 months. This study demonstrates that with appropriate expansion and isolation of zonal chondrocytes, stratified zonal chondrocyte implantation is able to facilitate restoration of articular cartilage zonal architecture and significantly enhance the functional repair as compared with current ACI treatment. With appropriate expansion and enrichment of zonal chondrocytes, stratified zonal chondrocyte implantation could represent a significant advancement over current ACI-based cartilage repair, with the potential to support quicker and better recovery.

Aerosol-cloud interactions remain one of the largest sources of uncertainty in estimates of anthropogenic climate forcing. Reducing aerosols to achieve air quality improvement and climate goals can cause unintended warming due to the weakening of aerosol cooling. Here we investigate the climate impacts of spatially optimized sulfur dioxide (SO2) emission reduction under a carbon-neutral pathway in China. We find that targeting reduction in highly polluted regions in China significantly suppresses the rise in effective radiative forcing due to aerosol-cloud interactions (ERFaci) during 2020-2060. Owing to the nonlinear aerosol-cloud interaction, the optimized emission reduction strategy limits the regional average increase in ERFaci of more than 0.89&#x2009;W&#x2009;m-2 to less than 0.13&#x2009;W&#x2009;m-2 in the short-term future during 2020-2040 and weakens the ERFaci increase by two-thirds in 2060 over China. These findings demonstrate the critical role of targeted emission control in mitigating short-term climate risks while pursuing air quality goals.

Cosmos is a vendor-facilitated platform created in collaboration with healthcare systems using electronic health records (EHRs) from Epic Systems Corporation. Participating organizations can use the platform to advance research and apply insights at the point of care. This manuscript outlines evolutions in the platform's infrastructure, growth of available data, and usage. Data from participating systems is sent via encrypted Health Level Seven Clinical Document Architecture to the Cosmos host at Epic Systems Corporation. Deduplicated data are stored in two relational Structured Query Language (SQL) databases, which can be accessed remotely. Aggregate counts from a limited dataset (LDS) are accessed through a no-code data visualization and analysis tool. Line-level data from an expert-determined de-identified dataset are accessed in a secure virtual computing environment. Data quality and user support frameworks facilitate a feedback loop improving data quality and researcher efficiency. Platform growth was measured as participating organization counts, data elements, and proportion of patient records with data spanning over 5 years. Medical literature was reviewed for peer-reviewed studies using Cosmos data. Over 330 organizations across Canada, Lebanon, Saudi Arabia, and the United States submit data to Cosmos. The platform includes more than 300 million deduplicated patient records, 39% of which have over 5 years of clinical data. Ongoing expansion of data elements within Cosmos has allowed the platform to serve as the data source for over 100 peer-reviewed studies across multiple disciplines. With its expanding size, tooling, and breadth of data elements, Cosmos may enable a wide range of study types. Cosmos remains subject to limitations such as variation in workflows, documentation error, and bias inherent to a population sourced from healthcare organizations using a single EHR vendor. Cosmos demonstrates a use case of vendor-facilitated collaboration to enable a broad spectrum of research.

Automated documentation tools are being rapidly adopted in healthcare and clinical workflows. Among these are AI-enabled ambient scribing products, which transcribe conversations between patients and healthcare providers, then produce clinical records using automatic speech recognition (ASR) and generative AI such as Large Language Models (LLMs). While research suggests these technologies can reduce clinical burden, safe and responsible deployment requires that these tools determine what captured information is appropriate to record and under which circumstances. This presents a contextual privacy challenge distinct from PII leakage or data memorization and remains largely untested. We address this gap by operationalizing privacy leakage as the inappropriate inclusion of third-party personal information in LLM-generated clinical notes. We construct a benchmark of transcripts containing private information with gold standard clinical notes by enriching patient metadata from the aci-bench corpus and injecting third-party personal information across six relationship types and seven information topics. We evaluate open weight LLaMA 3.1 8 and 70 B, Mixtral 8&#xd7;7B and 8&#xd7;22B, and proprietary Claude 3.5 Haiku and Sonnet models on note generation using prompts with varied privacy and structural requirements. All examined models leaked third-party information, and privacy instructions helped reduce leakage but proved neither complete nor robust as a solution. Models could generate privacy-infringing notes despite correctly identifying such information as inappropriate to share. Decomposing generation and privacy editing into separate steps could further reduce leakage, but only when privacy was defined with contextual specificity. No single mitigation eliminated leakage entirely, but combining approaches yielded the greatest reductions. Results emphasize the need to build privacy-by-design systems and develop evaluation strategies that reflect emerging information synthesis and sharing practices.

Background: Agaro-oligosaccharides (AOS) have been shown to modulate the gut microbiota in in vitro and animal studies; however, human evidence remains scarce. Methods: Herein, we conducted a four-week open-label, single-arm, non-randomized pilot trial in 18 healthy Japanese adults to examine the association of AOS intake at 200 mg/day with gut microbiota composition and bowel condition. Fecal samples collected before and after the intervention were analyzed using QIIME2-based 16S rRNA sequencing, and bowel condition was assessed with the Bristol Stool Form Scale. This study was registered in the UMIN Clinical Trials Registry (UMIN000056992). Results: AOS intake was not associated with significant changes in bowel condition. Gut microbiota analysis showed no significant alterations in overall community structure but revealed taxon-specific trends in the relative abundance of several bacterial taxa. Notably, nominal changes were observed in the abundance of the Ruminococcus gnavus group and Bacteroides uniformis after the intervention. In addition, quantitative PCR analysis showed an increase in 3,6-anhydro-L-galactose cycloisomerase (ACI) gene abundance after the intervention. Conclusions: These findings suggest that, in this exploratory pilot study, AOS intake was associated with a taxon-specific pattern in the gut microbiota. Further randomized controlled studies are needed to clarify the microbiota-related effects of AOS in humans.