Miracle-dz/UniFAR-FTUs huggingface dataset:
The Cholangiocarcinoma in the Young (CITY) Study: Tumor Biology, Treatment Patterns, and Survival Outcomes in Adolescent Young Adults With Cholangiocarcinoma

PURPOSE Increased awareness of the distinct tumor biology for adolescents and young adults (AYAs) with cancer has led to improvement in outcomes for this population. However, in cholangiocarcinoma (CCA), a paucity of data exist on the AYA population. To our knowledge, we present the largest study to date on AYA disease biology, treatment patterns, and survival outcomes in CCA. METHODS A multi-institutional cohort of patients with CCA diagnosed with intrahepatic cholangiocarcinoma (ICC) or extrahepatic cholangiocarcinoma (ECC) was used for analysis. Retrospective chart review was conducted on patients who were 50 years old and younger (young; n = 124) and older than 50 years (older; n = 723). RESULTS Among 1,039 patients screened, 847 patients met eligibility (72% ICC, 28% ECC). Young patients had a larger median tumor size at resection compared with older patients (4.2 v 3.6 cm; P = .048), more commonly had N1 disease (65% v 43%; P = .040), and were more likely to receive adjuvant therapy (odds ratio, 4.0; 95% CI, 1.64 to 9.74). Tumors of young patients were more likely to harbor an FGFR2 fusion, BRAF mutation, or ATM mutation (P < .05 for each). Young patients were more likely to receive palliative systemic therapy (96% v 69%; P < .001), targeted therapy (23% v 8%; P < .001), and treatment on a clinical trial (31% v 19%; P = .004). Among patients who presented with advanced disease, young patients had a higher median overall survival compared with their older counterparts (17.7 v 13.5 months; 95% CI, 12.6 to 22.6 v 11.4 to 14.8; P = .049). CONCLUSION Young patients with CCA had more advanced disease at resection, more commonly received both adjuvant and palliative therapies, and demonstrated improved survival compared with older patients. Given the low clinical trial enrollment and poor outcomes among some AYA cancer populations, data to the contrary in CCA are highly encouraging.
Feasibility, Outcomes, and Perceptions of a Virtual Group Exercise Program in Multiple Sclerosis

Background and Purpose: Individuals with multiple sclerosis (MS) frequently report low physical activity and psychosocial support due to concerns with transportation, time, finances, access to services, and lack of caregiver support. These barriers can be addressed by online group interventions; however, utility of such programs in individuals with MS has not been examined yet. The purpose of this retrospective study was, therefore, to (a) investigate the feasibility, safety, and outcomes of a virtual group exercise program in individuals with MS, and (b) explore the participant perceptions after the program. Methods: Retrospective data from the medical records of 17 individuals with MS (mean [SD] age = 53.5 [12.3] years, body mass index = 28.2 [7.2]) who completed the virtual 13-week group exercise program, pre- and posttraining functional status questionnaires, and the end-of-program feedback were extracted. The exercise program included aerobic, resistance, balance, and flexibility training components recommended for people with MS. Feasibility, safety, outcomes, and participant perceptions were determined by adherence to the prescribed daily exercise dosage, number of adverse events, within-group differences in self-reported functional status, and thematic analysis of the participant feedback, respectively. Results: Participants were adherent (79%), reported minimal adverse effects, and demonstrated significant changes (P < 0.05) in functional status posttraining. Several themes on the perceived barriers, facilitators, and suggestions for improvement were identified. Discussion and Conclusions: A virtual 13-week group exercise program can be feasible, safe, effective, and well received by individuals with MS. Future research should investigate the dose-response effectiveness of telehealth and compare various telehealth models of exercise training using large randomized controlled trials. Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1 available at: http://links.lww.com/JNPT/A434, which demonstrates an overview of the study).
Sea surface temperature, ocean color and wind forcing patterns in the Bay of La Paz, Gulf of California: Seasonal variability

Monthly climatologies are used to estimate the mean seasonal cycle of MODIS-Aqua satellite-derived sea surface temperature (SST), surface chlorophyll (Chl- a ) and their relationship with surface wind stress curl (from the Cross-Calibrate Multi-Platform, CCMP) in the Bay of La Paz located in the southwestern Gulf of California, a region identified as having high biological productivity and significant seasonal variability. Harmonic fit applied to the monthly climatologies of these variables indicate a best fit with annual and semi-annual constituents. The annual amplitude was the dominant signal in both SST and Chl- a , corresponding to the bay-wide seasonal cycle of warming and cooling associated with the influx of upwelled nutrient-rich coastal waters jointly with the water exchange between the bay and the Gulf of California. Empirical orthogonal function (EOF) decomposition yielded the annual and semi-annual patterns of the seasonal cycle that respond to wind forcing. The EOF 1 explained 93% of the SST variance and 48% of the Chl- a variance, showing a homogeneous variability of both variables across the bay and a strong thermal and biological gradient in the vicinity of the Gulf of California with their corresponding amplitude time series representing out-of-phase annual cycles, which corresponded to the regional dynamics of wind forcing pattern. The EOF 2 accounted for 6% of the SST variance and 31% of the Chl- a variance, which reached its peak during winter associated with the high Chl- a anomaly values (>1.5 mg m –3 ) observed along the coast. The intense biological productivity covaried strongly with the wind stress curl annual cycle ( R = 0.5, P < 0.05 ), suggesting that these Chl- a blooms could be associated with coastal currents and upwelling events regulated by the seasonal wind forcing pattern playing an essential role in the modulation of this quasi-permanent biophysical coupling observed in the Bay of La Paz during an annual cycle.
Long-term persistence and other treatment patterns among bio-naïve patients with Crohn’s disease treated with ustekinumab or adalimumab

Abstract Objective To estimate long-term persistence among bio-naïve patients with CD initiated on ustekinumab or adalimumab. Methods Adults with CD initiating ustekinumab or adalimumab (index date, between September 23, 2016 and August 1, 2019) were sampled from the IBM MarketScan Commercial Database. Patients without CD-indicated biologics (bio-naïve) and with no diagnoses for other autoimmune diseases 12 months pre-index date (baseline) were included. Cohorts were balanced on baseline characteristics with inverse probability of treatment weighting. Persistence was defined as the absence of therapy exposure gaps >120 days (ustekinumab) or >60 (adalimumab) between days of supply. Composite endpoints were persistence and being corticosteroid-free (no corticosteroids >14 days of supply after day 90 post-index) and persistence while on monotherapy (no immunomodulators/non-index biologics). Persistence was analyzed using Kaplan-Meier and Cox’s models. Results Ustekinumab and adalimumab cohorts included 671 and 2,975 patients. At 12 months post-index, ustekinumab patients were significantly more persistent (hazard ratio [HR] = 1.60; 95% confidence interval [CI] = 1.33–1.93), persistent while on monotherapy (HR = 1.43; 95% CI = 1.24–1.65), and trended toward being more persistent and corticosteroid-free (HR = 1.14; 95% CI = 0.99–1.30) vs adalimumab. At 24 months post-index, ustekinumab patients were significantly more persistent (HR = 1.66; 95% CI = 1.40–1.97), persistent while on monotherapy (HR = 1.44; 95% CI = 1.26–1.64), and persistent and corticosteroid-free (HR = 1.15; 95% CI = 1.01–1.31) vs adalimumab. Conclusions Bio-naïve patients with CD initiated on ustekinumab demonstrated significantly more persistence than patients initiated on adalimumab at 12 and 24 months of treatment. Long-term persistence is a measure of a drug’s real-world performance and findings may aid clinical decision-making. PLAIN LANGUAGE SUMMARY Choosing a treatment on which a patient can stay over a long period of time is key for the successful management of chronic conditions such as Crohn’s disease. Information on whether and how long patients stay on treatment can help physicians make the right therapeutic choice. This study examined whether adults with Crohn’s disease, who have not previously taken biologics, stay on treatment longer when given the biologic ustekinumab or adalimumab. At 12 and 24 months after starting the treatment, a larger proportion of patients were still using ustekinumab compared with adalimumab. The proportion of patients using the biologic without immunomodulators or other biologics was also higher with ustekinumab. The results suggest that patients without previous biologic experience stay on treatment longer with ustekinumab than with adalimumab.
ATG versus PTCy in matched unrelated donor haematopoietic stem cell transplantations with non‐myeloablative conditioning

Graft‐versus‐host disease (GvHD) is a serious complication of allogeneic haematopoietic stem cell transplantation (HSCT). Both anti‐thymocyte globulin (ATG) and post‐transplant cyclophosphamide (PTCy) are used as lymphocyte‐depleting strategies, yet a systematic comparison of transplantation outcomes between these two methods in matched unrelated donors (MUD) transplantations with non‐myeloablative conditioning (NMC) is lacking. Adult patients with haematological malignancies who had undergone MUD HSCT with NMC regimens between 2014 and 2021 at 2 centres in Amsterdam (ATG: n = 95, PTCy: n = 90), were included in this retrospective study. Patient characteristics were comparable between the groups. The cumulative incidence of acute GvHD grade II–IV was 48% in the ATG group compared to 21% in the PTCy group (p < 0.001). The 3‐year moderate/severe chronic GvHD was similar in both groups (p = 0.69). While the relapse rate was comparable between the groups (ATG 31% vs. PTCy 34%, p = 0.94), non‐relapse mortality tended to be higher in the ATG group (17% vs. 9%, p = 0.069). Overall survival was similar in both groups (p = 0.12). In conclusion, PTCy‐based regimens resulted in a significantly lower rate of acute GvHD than ATG‐containing regimens in MUD transplantations with NMC. Whether PTCy results in improved overall survival as compared to ATG needs to be elucidated in larger prospective studies.
Comparison of the effects PRICE and POLICE treatment protocols on ankle function in patients with ankle sprain

ABSTRACT BACKGROUND: Ankle sprain is a frequent reason for presentation to the emergency department. Current treatment modalities include Protection, Optimal Loading, Ice, Compression, and Elevation (POLICE) and Protection, Rest, Ice, Compression, and Elevation (PRICE). This study aimed to compare the effects of PRICE and POLICE treatment protocols. METHODS: This randomized controlled study was conducted between October 15, 2020, and October 15, 2021, at Ankara University’s Department of Emergency Medicine. Double-blind randomization was used to assign patients to either the POLICE or PRICE treatment groups. RESULTS: In total, 109 patients were included. In the POLICE group, the median difference between the American Orthopedic Foot and Ankle Scores on admission and the 14th day following the injury was 34.5 (IQR: 27.25–41.75), while that of the PRICE group was 24 (IQR: 15.5–35). In the POLICE group, the median value of the difference in the Foot and Ankle Disability Index scores on admission and the 14th day following the injury was 42 (IQR: 35.25–50), while that of the PRICE group was 31 (IQR: 22–41.5). CONCLUSION: The POLICE treatment protocol provided more effective and faster recovery than the PRICE treatment protocol.
Sex‐differences in the association of interleukin‐10 and interleukin‐12 variants with the progression of hepatitis B virus infection in Caucasians

Interleukin (IL)‐10 and IL‐12 contribute to immune responses against hepatitis B virus (HBV) infection. Polymorphisms in the IL‐10 and IL‐12A genes might affect the clinical outcome of HBV infection. We evaluated the association of IL‐10 rs1800896 and rs3024490, and IL‐12A rs568408 and rs2243115 with the progression of HBV infection and development of severe liver disease stages in a white European population.
Foot-and-mouth disease virus downregulates vacuolar protein sorting 28 to promote viral replication

ABSTRACT Vacuolar protein sorting 28 (Vps28), a component of the ESCRT-I (endosomal sorting complex required for transport I), plays an important role in the pathogen life cycle. Here, we investigated the reciprocal regulation between Vps28 and the foot-and-mouth disease virus (FMDV). Overexpression of Vps28 decreased FMDV replication. On the contrary, the knockdown of Vps28 increased viral replication. Subsequently, the mechanistic study showed that Vps28 destabilized the replication complex (RC) by associating with 3A rather than 2C protein. In addition, Vps28 targeted FMDV VP0, VP1, and VP3 for degradation to inhibit viral replication. To counteract this, FMDV utilized tactics to restrict Vps28 to promote viral replication. FMDV degraded Vps28 mainly through the ubiquitin-proteasome pathway. Additional data demonstrated that 2B and 3A proteins recruited E3 ubiquitin ligase tripartite motif-containing protein 21 to degrade Vps28 at Lys58 and Lys25, respectively, and FMDV 3Cpro degraded Vps28 through autophagy and its protease activity. Meantime, the 3Cpro-mediated Vps28 degradation principally alleviated the ability to inhibit viral propagation. Intriguingly, we also demonstrated that the N-terminal and C-terminal domains of Vps28 were responsible for the suppression of FMDV replication, which suggested the elaborated counteraction between FMDV and Vps28. Collectively, our results first investigate the role of ESCRTs in host defense against picornavirus and unveil underlying strategies utilized by FMDV to evade degradation machinery for triumphant propagation. IMPORTANCE ESCRT machinery plays positive roles in virus entry, replication, and budding. However, little has been reported on its negative regulation effects during viral infection. Here, we uncovered the novel roles of ESCRT-I subunit Vps28 on FMDV replication. The data indicated that Vps28 destabilized the RC and impaired viral structural proteins VP0, VP1, and VP3 to inhibit viral replication. To counteract this, FMDV hijacked intracellular protein degradation pathways to downregulate Vps28 expression and thus promoted viral replication. Our findings provide insights into how ESCRT regulates pathogen life cycles and elucidate additional information regarding FMDV counteraction of host antiviral activity. ESCRT machinery plays positive roles in virus entry, replication, and budding. However, little has been reported on its negative regulation effects during viral infection. Here, we uncovered the novel roles of ESCRT-I subunit Vps28 on FMDV replication. The data indicated that Vps28 destabilized the RC and impaired viral structural proteins VP0, VP1, and VP3 to inhibit viral replication. To counteract this, FMDV hijacked intracellular protein degradation pathways to downregulate Vps28 expression and thus promoted viral replication. Our findings provide insights into how ESCRT regulates pathogen life cycles and elucidate additional information regarding FMDV counteraction of host antiviral activity.
Acute Effect of Heavy Weightlifting on the Pelvic Floor Muscles in Strength-Trained Women: An Experimental Crossover Study

ABSTRACT Introduction/Purpose Heavy lifting may produce strain on the pelvic floor muscles (PFM) due to high increases in intra-abdominal pressure, but knowledge of the impact of weightlifting on the PFM is lacking. Therefore, this study aimed to investigate acute effects of heavy weightlifting on the PFM in strength-trained women and whether general strength in whole-body exercises correlated to PFM strength. Methods Forty-seven nulliparous women between 18 and 35 yr who regularly performed weightlifting and were able to lift their own body weight × 1.2 in back squat and 1.5 in deadlift were included in this experimental crossover study. They participated in baseline evaluations (questionnaire/measurements of background characteristics and pelvic floor disorders, one-repetition maximum (1RM) tests in back squat and deadlift) and one test day where they were randomized to start with 60 min of weightlifting (four sets of four repetitions at 75%–85% of 1RM in back squat and deadlift) or seated rest of 60 min. Vaginal pressure measurements of PFM resting pressure, strength, and endurance and surface electromyography measurements of PFM resting activity were performed before/after weightlifting and rest. Results No statistically significant differences were found when comparing the change in PFM resting pressure, strength, endurance, and resting activity after heavy weightlifting and rest. There were no statistically significant correlations between PFM strength and maximum (1RM) or relative strength (1RM/bodyweight) in either back squat or deadlift. Conclusions Our results imply that heavy weightlifting is well tolerated by the PFM in short term among young, nulliparous, and strength-trained women. Strength in whole-body exercises was not correlated to PFM strength.
Decongestion strategies in patients presenting with acutely decompensated heart failure: A worldwide survey among physicians

Decongestion strategies for acute decompensated heart failure (ADHF) characterized by volume overload differ widely. The aim of this independent international academic web‐based survey was to capture the therapeutic strategies that physicians use to treat ADHF and to assess differences in therapeutic approaches between cardiologists versus non‐cardiologists.
Double exponentially weighted moving average control chart with supplementary runs-rules

ABSTRACT Enhancing the sensitivity of control charts for detecting small process shift is desirable and may be done in different ways. In this paper, we propose the double exponentially weighted moving average (DEWMA) control chart using the 2-of-2 and 1-of-1 or 2-of-2 runs-rules schemes for monitoring process mean shifts. The performances of the resulting control schemes are investigated in terms of the average run-length (), standard deviation of the run-length () and selective percentiles of the run-length (). In addition, the overall performance of the proposed runs-rules charts are examined and compared with those of the existing charts in terms of the , average extra quadratic loss (), average ratio of the average run-length () and performance comparison index () values. It is observed that the proposed control schemes are more efficient in many situations and improve the ability of the existing DEWMA schemes in detecting small, moderate and large mean shifts.
Examining trauma cognition change trajectories among initial PTSD treatment non-optimal responders: a potential avenue to guide subsequent treatment selection

ABSTRACT Background: Despite their general effectiveness, 14-50% of individuals do not fully respond to evidence-based treatments for posttraumatic stress disorder (PTSD). Although changes in negative posttrauma cognitions (NPCs) are considered a likely PTSD treatment mechanism, less is known about how NPCs change among individuals who continue to be symptomatic following treatment (non-optimal responders). Objective: The objective of this study was to examine NPC change trajectories among individuals who were determined to be non-optimally responsive to intensive PTSD treatment. Method: Using a 3-week Cognitive Processing Therapy-based intensive PTSD treatment sample (ITP; N = 243), the present study examined the number of distinct NPC change trajectories among non-optimal responders via Group Based Trajectory Modeling and assessed predictors of non-optimal responders’ NPC change trajectory membership. Analyses were replicated in a separate 2-week ITP sample (N = 215). Results: In both non-optimal responder samples, two trajectories emerged; a no NPC change group which represented those with an overall lack of NPC change throughout treatment and an NPC change group which represented those with an overall reduction of NPCs occurring primarily later in treatment. Changes in PTSD symptom severity during treatment was the only consistent predictor of NPC change trajectory group membership among treatment non-optimal responders across ITPs. Conclusions: Findings suggest NPC change among non-optimal responders is nuanced and may inform subsequent intervention selection, resulting in testable hypotheses for future research. HIGHLIGHTS Throughout intensive PTSD treatment, non-optimal responders exhibited two distinct negative posttrauma cognition change trajectories: (1) no change, and (2) slow change. Changes in PTSD symptom severity during treatment consistently predicted non-optimal responders’ trajectory of change in negative posttrauma cognitions. Additional research is needed to explore how nuances of negative posttrauma cognition change may inform subsequent treatment intervention in initial non-optimal responders.
Supplement use in relation to dietary intake in pregnancy: an analysis of the Swedish GraviD cohort

Abstract We aimed to study supplement use in relation to dietary intake among pregnant women in Sweden, and adherence to the Nordic Nutrition Recommendations among supplement and non-supplement users. Pregnant women were recruited at registration to antenatal care in 2013–2014. In third trimester, supplement use was collected using a questionnaire, and dietary intake was collected using a FFQ. The majority (64 %) of the 1044 women reported use of one or more supplements. Among all, 0–23 % reported dietary intakes above recommended intake (RI) of vitamin D, folate, Fe and Se. Median dietary intakes of thiamine (1·4 v. 1·3 mg P = 0·013), phosphorus (1482 v. 1440 mg P = 0·007), folate (327 v. 316 µg P = 0·02), Fe (12 v. 11·5 mg P = 0·009), Mg (361 v. 346 mg P < 0·001) and Zn (10·7 v. 10·4 mg P = 0·01) were higher among supplement users compared with non-users. Larger proportions of supplement users than non-users adhered to RI of dietary intakes of thiamine (42 % v. 35 % P = 0·04) and Mg (75 % v. 69 % P = 0·05). Among non-users, a minority had dietary intakes above RI for vitamin D (6 %), folate (10 %) and Fe (21 %). The majority (75–100 %) of supplement users had total intakes above RI for most nutrients. In conclusion, supplement use contributed substantially to reaching RI for vitamin D, folate and Fe. Supplement users had a higher dietary intake of several nutrients than non-users. This highlights that non-supplement users are at risk of inadequate nutrient intakes during pregnancy, suggesting a need for heightened awareness of nutritional adequacy for pregnant women.