bluuebunny/crossref_metadata_2025 huggingface dataset:
Association Between Total Genotype Score and Muscle Injuries in Top-Level Football Players: a Pilot Study
Authors: Massidda Myosotis , Flore Laura , Cugia Paolo , Piras Francesco , Scorcu Marco , Kikuchi Naoki , Cięszczyk Pawel , Maciejewska-Skrendo Agnieszka , Tocco Filippo , Calò Carla Maria
Published: March 2024

Background

Recently, genetic predisposition to injury has become a popular area of research and the association between a few single nucleotide polymorphisms (SNPs) and the susceptibility to develop musculoskeletal injuries has been shown. This pilot study aimed to investigate the combined effect of common gene polymorphisms previously associated with muscle injuries in Italian soccer players.

Results

A total of 64 Italian male top football players (age 23.1 ± 5.5 years; stature 180.2 ± 7.4 cm; weight 73.0 ± 7.9 kg) were genotyped for four gene polymorphisms [ACE I/D (rs4341), ACTN3 c.1729C > T (rs1815739), COL5A1 C > T (rs2722) and MCT1 c.1470A > T (rs1049434)].

Muscle injuries were gathered for 10 years (2009–2019). Buccal swabs were used to obtain genomic DNA, and the PCR method was used to genotype the samples. The combined influence of the four polymorphisms studied was calculated using a total genotype score (TGS: from 0 to 100 arbitrary units; a.u.). A genotype score (GS) of 2 was assigned to the “protective” genotype for injuries, a GS of 1 was assigned to the heterozygous genotype while a GS of 0 was assigned to the “worst” genotype.

The distribution of genotype frequencies in the ACE I/D (rs4341), ACTN3 c.1729C > T (rs1815739) and MCT1 c.1470A > T (rs1049434) polymorphisms was different between non-injured and injured football players (p = 0.001; p = 0.016 and p = 0.005, respectively). The incidence of muscle injuries was significantly different among the ACE I/D (rs4341), ACTN3 c.1729C > T (rs1815739) and COL5A1 C > T (rs2722) genotype groups, showing a lower incidence of injuries in the “protective” genotype than “worse” genotype (ACE, p < 0.001; ACTN3, p = 0.005) or intermediate genotype (COL5A1, p = 0.029).

The mean TGS in non-injured football players (63.7 ± 13.0 a.u.) was different from that of injured football players (42.5 ± 12.5 a.u., p < 0.001). There was a TGS cut-off point (56.2 a.u.) to discriminate non-injured from injured football players. Players with a TGS beyond this cut-off had an odds ratio of 3.5 (95%CI 1.8–6.8; p < 0.001) to suffer an injury when compared with players with lower TGS.

Conclusions

These preliminary data suggest that carrying a high number of "protective" gene variants could influence an individual's susceptibility to developing muscle injuries in football. Adapting the training load parameters to the athletes’ genetic profile represents today the new frontier of the methodology of training.
Return and volatility spillovers between non-fungible tokens and conventional currencies: evidence from the TVP-VAR model
Authors: Yousaf Imran , Youssef Manel , Gubareva Mariya
Published: March 2024

This study investigates the static and dynamic return and volatility spillovers between non-fungible tokens (NFTs) and conventional currencies using the time-varying parameter vector autoregressions approach. We reveal that the total connectedness between these markets is weak, implying that investors may increase the diversification benefits of their multicurrency portfolios by adding NFTs. We also find that NFTs are net transmitters of both return and volatility spillovers; however, in the case of return spillovers, the influence of NFTs on conventional currencies is more pronounced than that of volatility shock transmissions. The dynamic exercise reveals that the returns and volatility spillovers vary over time, largely increasing during the onset of the Covid-19 crisis, which deeply affected the relationship between NFTs and the conventional currencies markets. Our findings are useful for currency traders and NFT investors seeking to build effective cross-currency and cross-asset hedge strategies during systemic crises.
Application of hospital–community–home linkage management model in patients with type 2 diabetic nephropathy
Authors: Xu Hong-Mei , Zhai Yan-Ping , Zhu Wen-Juan , Li Min , Wu Zhi-Ping , Wang Peng , Wang Xue-Jing
Published: March 2024

Objective

To explore the effect of the hospital–community–home (HCH) linkage management mode in patients with type 2 diabetic nephropathy (DN).

Method

A total of 80 patients with type 2 DN hospitalised in the Department of Nephrology of our hospital between July 2021 and June 2022 were recruited and subsequently divided into the observation group and the control group using the random number table method, with 40 patients in each group. The control group received routine health education and discharge guidance. The HCH linkage management model was implemented for the observation group based on routine care. The improvements in compliance behaviour, biochemical parameters of renal function, blood glucose level and self-management ability were compared before the intervention and at 3 and 6 months after the intervention.

Results

After the intervention, the scores for compliance behaviour of the observation group were better than those of the control group, with a statistically significant difference (P < 0.05). The biochemical indicators of renal function and blood glucose level were significantly lower in the observation group compared with in the control group, with a statistically significant difference (P < 0.05). After the intervention, the observation group showed a great improvement in self-management ability and cognition of the disease, with significant differences (P < 0.05).

Conclusion

The HCH linkage management mode can improve the compliance behaviour of patients with type 2 DN, effectively improve the renal function and blood sugar level of patients, enhance the self-management ability and cognition of the disease and delay the development of the disease.
Uterine smooth muscle tumors of uncertain malignant potential: a retrospective evaluation of clinical pathology and immunohistochemistry features
Authors: Akbarzadeh-Jahromi Mojgan , Todarbary Nafiseh , Aslani Fatemeh Sari , Najib Fatemehsadat , Zare Marjan , Amirmoezi Fatemeh
Published: March 2024

Background

Uterine smooth muscle tumor of uncertain malignant potential (STUMP) is a group of uterine smooth muscle tumors which cannot be classified as a subtype of leiomyoma or leiomyosarcoma. Diagnosis, prognosis, and treatment of these tumors are challenging due to recurrence, potential of malignancy, and metastasis.

Methods

A retrospective cohort study was conducted in southern Iran during 2011 to 2020. We included records of 21 patients with STUMP and 24 patients with leiomyoma by simple randomized sampling in the tertiary health care centers in Shiraz, southern Iran. Slides were reviewed by an expert pathologist for examining mitosis, necrosis, and atypia, and also proper blocks were selected for immunohistochemistry (IHC) staining.

Results

From 45 participants, 21 (46.7%) and 24 (53.3%) patients were in the STUMP and normal leiomyoma groups, respectively. Odds ratio and 95% confidence interval (OR (95% C.I)) of pathologic size in the range of 5–10 cm was significantly higher in the STUMP group compared with normal leiomyoma. (CI: 7.22 (1.44–36.22)). Additionally, hyaline necrosis 0.05 (0.0-0.91), mild to moderate atypia 0.02 (0.0-0.4), moderate to severe atypia 0.01 (0.0-0.22), focal atypia 0.01 (0-0.26) and diffuse atypia 0.01 (0-0.26) were significantly fewer in normal leiomyoma compared to the STUMP group. Negative P16 0.01 (0.0007-0.24) and negative Bcl2 0.22 (0.06–0.81) were significantly higher in the normal leiomyoma group compared with the STUMP group. The cut-off points for predicting STUMP were 2.5% (sensitivity = 62% and specificity = 100%) and 45% (sensitivity = 43% and specificity = 96%) for P16 and bcl2, respectively.

Conclusion

The category and management of STUMP continues to progress. The diagnosis for STUMP mainly depends on the histopathological manifestations. No single IHC marker such as P53, P16, and Bcl-2 has proved robust enough in separating STUMP from other leiomyoma variants; however, according to our study, we suggest combination use of P16 and Bcl-2 (cut off 2.5 and 45%, respectively) to distinguish equivocal cases of STUMP.
Trends in stroke severity at hospital admission and rehabilitation discharge before and during the COVID-19 pandemic in Hesse, Germany: a register-based study
Authors: Belau Matthias Hans , Misselwitz Björn , Meyding-Lamadé Uta , Bassa Burc
Published: March 2024

Background

The COVID-19 pandemic has affected acute stroke care, resulting in a decrease in stroke admissions worldwide. We examined trends in stroke severity at hospital admission, including (1) probable need for rehabilitation (National Institutes of Health Stroke Scale score > 6 points) and (2) probable need for assistance (modified Rankin Scale score > 2 points), and discharge to rehabilitation after acute care among inpatients with acute ischemic stroke and intracerebral hemorrhage.

Methods

We compared quality assurance data for acute ischemic stroke and intracerebral hemorrhage during the pandemic with the period before the pandemic in Hesse, Germany, using logistic regression analyses.

Results

Fewer inpatients with a probable need for rehabilitation were present at the beginning of the second wave of the COVID-19 pandemic in September 2020 (adjusted OR (aOR) 0.85, 95% CI [0.73, 0.99]), at the end of the second national lockdown in May 2021 (aOR 0.81, 95% CI [0.70, 0.94]), and at the approaching peak of COVID-19 wave 4 in November 2021 (aOR 0.79, 95% CI [0.68, 091]). Rates of probable need for assistance were significantly lower at the beginning of COVID-19 wave 2 in August 2020 (aOR 0.87, 95% CI [0.77, 0.99]) and at the beginning of COVID-19 wave 3 in March 2021 (aOR 0.80, 95% CI [0.71, 0.91]). Rates of discharge to rehabilitation were lower from the beginning in October 2020 to the peak of COVID-19 wave 2 in December 2020 (aOR 0.83, 95% CI [0.77, 0.90]), at the beginning and end of COVID-19 wave 3 in March 2021 and May 2021 (aOR 0.86, 95% CI [0.79, 0.92]), respectively, and at the beginning of COVID-19 wave 4 in October 2021 (aOR 0.86, 95% CI [0.76, 0.98]).

Conclusions

The results suggest that the COVID-19 pandemic had an impact on stroke management during the pandemic, but the absolute difference in stroke severity at hospital admission and discharge to rehabilitation was small.
Quality analysis and antioxidant activity of different types of tea powder
Authors: Ye Yutong , Ai Zeyi , Li Ronglin , Tian Yang , Yang Yiyang
Published: March 2024

As a natural product with health benefits, tea powder (TP) is widely used in food processing field. In order to explore sensory evaluation, quality components and antioxidant activities among different types of TP, matcha TP, Huangjinya green TP, oolong TP, black TP and Pu-erh TP were used as the research objects. Our results showed that total scores of sensory evaluation of unfermented TPs were higher than those of fermented TPs, whilst the colour of those unfermented TPs was more bright. Furthermore, taste attributes showed that sweetness was conducive to the formation of the taste of black TP, and aftertaste-bitterness was beneficial to matcha and Pu-erh TP. Umami was suggested as a vital contributing factor to the mellow taste of Huangjinya green TP, while sourness and bitterness were not propitious to form the taste quality of tea powder. The non-volatile quality components analysis revealed that tea powders with more fermentation usually contained fewer amino acids and catechins, but glutamate and gamma-aminobutyric acid were higher in black TP than in oolong TP. Theanine, glutamic acid and arginine were the main iconic components affecting the amino acid composition of different types of tea powder in our study. Meanwhile, the contents of ester catechins (ECG, EGC, EGCG) in black TP and Pu-erh TP were significantly lower than those in green TP and oolong TP. In addition, the free radical scavenging ability of unfermented TPs were stronger than that of fermented TPs. Therefore, to maximize the health benefits and sensory attributes of different types of TP, the use of unfermented tea powder is recommended. However, different manufacturing process of tea powder can enrich the taste of tea foods, thus giving people more choices.

Graphical Abstract
Technologies of gene editing and related clinical trials for the treatment of genetic and acquired diseases: a systematic review
Authors: Sharaf-Eldin Wessam
Published: March 2024

Background

Gene editing can produce irreversible permanent changes to the genetic material at predetermined sequences, avoiding random integration, which is the major drawback of classical gene therapy. The technology has invaded all approaches of genetic engineering and biotechnology with versatile applications in agriculture, industry, and medicine.

Main body

The present review displays the different approaches and mechanisms of gene editing. Special emphasis has been given to the technology therapeutic applications where all registered clinical trials have been addressed. The Islamic ethical concerns of gene editing have also been highlighted.

Conclusion

The great advantages of gene editing technology, coupled with the splendid efforts of scientists to develop systems with superior efficacy and safety would provide an effective avenue for treating a wide range of human diseases in the near future.
Assessing physicians’ knowledge, attitude, and practice on anticoagulant therapy in non-valvular atrial fibrillation: Syrian insights
Authors: Swed Sarya , Bohsas Haidara , Alibrahim Hidar , Nasif Mohamad Nour , Abouainain Yasmeen , Jawish Nagham , Ishak Angela , Dibah Bassel , Mahmoud Eva , Mahfoud Suzanne , Sawaf Bisher , Hafez Wael , El Said Nouran Omar , Wahsh Engy Ahmed
Published: March 2024

Background

Atrial fibrillation (AF) is the most prevalent cardiac condition linked to increased mortality due to complications such as stroke. Oral anticoagulant (OAC) is the mainstay in preventing cerebrovascular accidents in patients with AF. Recent evidence identified gaps in physician’s knowledge in diagnosing and managing patients with AF. This study aims to assess Syrian physicians’ knowledge, attitude, and practices regarding the use of anticoagulant therapy in non-valvular AF (NVAF) patients. A cross-sectional study was conducted using a validated web-based questionnaire, which included 56 items separated into four sections that collected information about demographics, knowledge, attitude, and practices. Chi-square and Kruskal Wallis were performed to analyze the statistical relationships between the knowledge, attitude, practice, and demographic variables.

Results

A total of 497 participants completed the survey, of which 62.6% were between the ages of 25 and 35. The average participant scores for knowledge, attitude, and practices were (48.18 ± 21.57), (81.54 ± 9.26), and (62.83 ± 12.42), respectively. Participants who demonstrated good understanding, a positive attitude, and good practices were 22.3%, 87.3%, and 25.4%, respectively. The fear of bleeding was identified as the most significant barrier to initiating anticoagulant medication in AF patients (55.5%). Doctors who attended training had a better knowledge score than those who did not (mean ± S.D. = 57.24 ± 20.7). Participants who stated that over 70% of their AF patients use aspirin received the highest attitude score (mean ± S.D = 86.98 ± 21.17). PhD participants reported higher practice scores than those with other educational backgrounds (mean ± S.D = 73.96 ± 11.3).

Conclusion

This research showed that primary care physicians in Syria had optimistic views regarding OAC therapy, suggesting that training interventions targeting physicians may lead to improvement in the treatment of patients with NVAF in Syria.
Staged Norwood operation for patients with hypoplastic left heart syndrome and cor triatriatum: a report of two cases
Authors: Iijima Yukino , Hoashi Takaya , Kojima Takuro , Nagase Haruhiro , Fuchigami Yuji , Suzuki Takaaki
Published: March 2024

Two patients with hypoplastic left heart syndrome (HLHS) concomitant with cor triatriatum underwent the staged Norwood procedure following hybrid palliation. Cor triatriatum was diagnosed after birth in both cases. Case 1 with aortic stenosis and mitral atresia underwent bilateral pulmonary artery banding at 2 days of age. Subsequently, balloon atrial septostomy was conducted at 21 days of age due to hypoxia and increased intra-atrial pressure gradient. At 2 months of age, concomitant Norwood operation, cor triatriatum repair, and tricuspid valve repair were successfully performed. She has suffered from branch pulmonary artery hypoplasia since then; thus, Fontan operation was out of indication. Case 2 with aortic stenosis and mitral stenosis underwent bilateral pulmonary artery banding at 6 days of age. After that, the patient’s hemodynamic condition remained stable. The Norwood operation concomitant with cor triatriatum repair was performed at 2 months of age. However, during the procedure, massive pulmonary edema and hemorrhage occurred right after the initiation of cardiopulmonary bypass. She could not be weaned from cardiopulmonary bypass.
How can primary care benefit from digital health applications? – a quantitative, explorative survey on attitudes and experiences of general practitioners in Germany
Authors: Wangler Julian , Jansky Michael
Published: March 2024

Background

Since 2020, physicians in Germany have the possibility of prescribing approved digital health applications (DHAs) with the costs covered by the health system – a step that was unique in the world at that time and still is. So far, there have been hardly any studies that shed light on the possible applications of DHAs in the context of primary care and take stock of the benefits and potential for optimization. In 2022, a quantitative survey was carried out. The aim was to determine what attitudes, experiences and expectations GPs have with regard to the use of DHAs, under what conditions they are willing to integrate them into health care, and what experience they have already gained.

Methods

The focus was on a large-scale survey of GPs. Between spring and summer 2022, all 18,914 GPs in the federal states of Baden-Württemberg, Hesse, Lower Saxony, Rhineland-Palatinate and Saarland were invited to an online survey. 5,868 questionnaires were included in the evaluation (response rate: 31%). A t-test on independent samples was used to determine significant differences between two groups.

Results

68% of those surveyed are positive about DHAs and consider them to be reliable (69%) and safe (63%) applications that can generate efficiency benefits for the doctor-patient relationship. 24% trust themselves to competently advise patients on DHAs. 14% have already prescribed DHAs, 13% plan to do so. 85% of doctors with DHA experience rate the prescribed applications as (very) useful. Observed health care effects relate primarily to the improvement in compliance (94%), mobility (93%), and education (93%), as well as weight reduction (83%). Among other things, a further optimization of usability (59%), systematic further training of doctors on DHAs (53%) and the expansion of gamification elements (49%) are suggested. GPs lack well-founded information with regard to DHAs (52%).

Conclusion

For GPs, DHAs can be effective tools to encourage patients in their personal responsibility, compliance and motivation to behave in a health-conscious manner and to strengthen prevention in the primary care setting. Where DHAs have been used in a practical context so far, widespread positive health care effects are noticeable. Most respondents do not dare to give patients competent advice on available applications. Comprehensive training courses that provide information about the framework conditions, strategies and advantages of using DHAs appear to be important. There is also a need for more well-founded sources of information and research for doctors to select suitable applications in a targeted manner. GPs see significant added value in DHAs compared to conventional health apps. In order for DHAs to be effectively implemented in primary care, it is important to better inform GPs about the legal basis and possible applications as well as to address their concerns.
Clinician treatment choices for post-traumatic stress disorder: ambassadors survey of psychiatrists in 39 European countries
Authors: Rojnic Kuzman Martina , Padberg Frank , Amann Benedikt L. , Schouler-Ocak Meryam , Bajic Zarko , Melartin Tarja , James Adrian , Beezhold Julian , Artigue Gómez Jordi , Arango Celso , Jendricko Tihana , Ismayilov Jamila , Flannery William , Chumakov Egor , Başar Koray , Vahip Simavi , Dudek Dominika , Samochowiec Jerzy , Mihajlovic Goran , Rota Fulvia , Stoppe Gabriela , Dom Geert , Catthoor Kirsten , Chkonia Eka , Heitor Dos Santos Maria João , Telles Diogo , Falkai Peter , Courtet Philippe , Patarák Michal , Izakova Lubomira , Skugarevski Oleg , Barjaktarov Stojan , Babic Dragan , Racetovic Goran , Fiorillo Andrea , Carpiniello Bernardo , Taube Maris , Melamed Yuval , Chihai Jana , Cozman Doina Constanta Maria , Mohr Pavel , Szekeres György , Delic Mirjana , Mazaliauskienė Ramunė , Tomcuk Aleksandar , Maruta Nataliya , Gorwood Philip
Published: March 2024

Background

Considering the recently growing number of potentially traumatic events in Europe, the European Psychiatric Association undertook a study to investigate clinicians’ treatment choices for post-traumatic stress disorder (PTSD).

Methods

The case-based analysis included 611 participants, who correctly classified the vignette as a case of PTSD, from Central/ Eastern Europe (CEE) (n = 279), Southern Europe (SE) (n = 92), Northern Europe (NE) (n = 92), and Western Europe (WE) (N = 148).

Results

About 82% woulduse antidepressants (sertraline being the most preferred one). Benzodiazepines and antipsychotics were significantly more frequently recommended by participants from CEE (33 and 4%, respectively), compared to participants from NE (11 and 0%) and SE (9% and 3%). About 52% of clinicians recommended trauma-focused cognitive behavior therapy and 35% psychoeducation, irrespective of their origin. In the latent class analysis, we identified four distinct “profiles” of clinicians. In Class 1 (N = 367), psychiatrists would less often recommend any antidepressants. In Class 2 (N = 51), clinicians would recommend trazodone and prolonged exposure therapy. In Class 3 (N = 65), they propose mirtazapine and eye movement desensitization reprocessing therapy. In Class 4 (N = 128), clinicians propose different types of medications and cognitive processing therapy. About 50.1% of participants in each region stated they do not adhere to recognized treatment guidelines.

Conclusions

Clinicians’ decisions for PTSD are broadly similar among European psychiatrists, but regional differences suggest the need for more dialogue and education to harmonize practice across Europe and promote the use of guidelines.
US Food and Drug Administration Approval Summary: Talazoparib in Combination With Enzalutamide for Treatment of Patients With Homologous Recombination Repair Gene-Mutated Metastatic Castration-Resistant Prostate Cancer
Authors: Heiss Brian L. , Chang Elaine , Gao Xin , Truong Tien , Brave Michael H. , Bloomquist Erik , Shah Ankit , Hamed Salaheldin , Kraft Jeffrey , Chiu Haw-Jyh , Ricks Tiffany K. , Tilley Amy , Pierce William F. , Tang Liuya , Abukhdeir Abdelrahmman , Kalavar Shyam , Philip Reena , Tang Shenghui , Pazdur Richard , Amiri-Kordestani Laleh , Kluetz Paul G. , Suzman Daniel L.
Published: March 2024

PURPOSE

The US Food and Drug Administration (FDA) approved talazoparib with enzalutamide for first-line treatment of patients with homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC).

PATIENTS AND METHODS

The approval was based on the HRR gene-mutated (HRRm) population of TALAPRO-2, a randomized, double-blind trial that randomly assigned 1,035 patients with mCRPC to receive enzalutamide with either talazoparib or placebo. Two cohorts enrolled sequentially: an all-comer population (Cohort 1), followed by an HRRm-only population (Cohort 2). The independent primary end points were radiographic progression-free survival (rPFS) per blinded independent central review (BICR) in Cohort 1 (all-comers) and in the combined HRRm population (all HRRm patients from Cohorts 1 and 2). Overall survival (OS) was a key secondary end point.

RESULTS

A statistically significant improvement in rPFS by BICR was demonstrated in both the all-comers cohort and the combined HRRm population, with hazard ratio (HR) of 0.63 (95% CI, 0.51 to 0.78; P < .0001) and 0.45 (95% CI, 0.33 to 0.61; P < .0001), respectively. In an exploratory analysis of the 155 patients with BRCA-mutated ( BRCAm) mCRPC, rPFS HR was 0.20 (95% CI, 0.11 to 0.36). In the non-HRRm/unknown stratum of Cohort 1 (n = 636), the rPFS HR was 0.70 (95% CI, 0.54 to 0.89). OS was immature.

CONCLUSION

Despite a statistically significant rPFS improvement in the all-comer cohort, FDA did not consider the magnitude of rPFS clinically meaningful in the context of the broad indication, combination treatment, and safety profile. Approval was therefore limited to patients with HRRm mCRPC, for whom there was a statistically significant and clinically meaningful improvement in rPFS and favorable OS results. This represents the first approval for the first-line treatment of patients with HRRm mCRPC.
Pembrolizumab Versus Placebo as Adjuvant Therapy in Resected Stage IIB or IIC Melanoma: Final Analysis of Distant Metastasis-Free Survival in the Phase III KEYNOTE-716 Study
Authors: Luke Jason J. , Ascierto Paolo A. , Khattak Muhammad A. , de la Cruz Merino Luis , Del Vecchio Michele , Rutkowski Piotr , Spagnolo Francesco , Mackiewicz Jacek , Chiarion-Sileni Vanna , Kirkwood John M. , Robert Caroline , Grob Jean-Jacques , de Galitiis Federica , Schadendorf Dirk , Carlino Matteo S. , Wu Xi Lawrence , Fukunaga-Kalabis Mizuho , Krepler Clemens , Eggermont Alexander M.M. , Long Georgina V.
Published: March 2024

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.

Pembrolizumab adjuvant therapy was shown to significantly improve recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) in patients with resected stage IIB or IIC melanoma in earlier analyses of the randomized, double-blind, phase III KEYNOTE-716 study (ClinicalTrials.gov identifier: NCT03553836 ). We report results of the protocol-specified final analysis of DMFS for KEYNOTE-716. Overall, 976 patients were randomly allocated to pembrolizumab (n = 487) or placebo (n = 489). As of January 4, 2023, median follow-up was 39.4 months (range, 26.0-51.4 months). The median DMFS was not reached in either treatment group, and the estimated 36-month DMFS was 84.4% for pembrolizumab and 74.7% for placebo (hazard ratio [HR], 0.59 [95% CI, 0.44 to 0.79]). The median RFS was not reached in either treatment group, and the estimated 36-month RFS was 76.2% for pembrolizumab and 63.4% for placebo (HR, 0.62 [95% CI, 0.49 to 0.79]). DMFS and RFS results were consistent across most prespecified subgroups, including stage IIB and stage IIC melanoma. The safety profile of pembrolizumab was manageable and consistent with previous reports. These results continue to support the use of pembrolizumab adjuvant therapy in patients with resected stage IIB or IIC melanoma.
Promise and Perils of Large Language Models for Cancer Survivorship and Supportive Care
Authors: Bitterman Danielle S. , Downing Andrea , Maués Julia , Lustberg Maryam
Published: March 2024

A call to action to bring stakeholders together to plan for the future of LLM-enhanced cancer survivorship.
National Wounds and Gendered Harm: Reframing Abortion Pain in The Worst of Times
Authors: O’Connell Alex
Published: March 2024

In light of abortion’s recurrent political centrality in the United States, examining abortion narratives remains critically urgent. This article analyzes the abortion narratives found in the 1993 anthology The Worst of Times compiled by Patricia G. Miller, which collects individual stories of illegal abortions from the post–World War II years. It analyzes these narratives in the context of the postwar period’s growing sensational political fascination with abortion pain, alongside the second-wave feminist positioning of abortion as the paramount feminist issue and inherent basis of feminist community. Against these discourses, the semi-anonymous narrators of The Worst of Times disrupt hierarchized, universal, and exclusionary models of pain. Rather, this article argues that, in constructing life writing centered around the painful experience of illegal abortion, the narrators’ experiences cohere into relational clusters that evince commonalities while also maintaining differences. In engaging with their painful abortion experiences, these narratives reshape the medical, national, and feminist power structures that attempted to define the pain that abortion signified. In a moment when abortion legislation faces continued assaults, these narratives invite a consideration of how the embodied, personal pain of abortion can facilitate creative models of community that rethink the power structures that restrict reproductive autonomy.
Borders, Human Itineraries, and All Our Relation
Authors: Adeyemo Dele , Diaz Natalie , Kisukidi Nadia Yala , Walcott Rinaldo , Sharpe Christina
Published: March 2024

The first annual Alchemy Lecture brings four deep and agile writers from different geographies and disciplines into vibrant conversation on a topic of urgent relevance: humans and borders. Borders, Human Itineraries, and All Our Relation captures and expands those conversations in insightful, passionate ways. Architect, artist, and urban theorist Dele Adeyemo (UK/Nigeria) calls attention to the complexity of Black infrastructures, questioning how “the environments that surround us condition the possibility of our being.” Poet Natalie Diaz (US/Mojave/Akimel O’otham) writes, “Like story, migration is the sensual movement of knowledge,” and asks, “What is the language we need to live right now?” Philosopher Nadia Yala Kisukidi (France) suggests there is no diasporic life “without the dynamics of fabulation, where we pass down, from generation to generation, the stories of our ancestors who walked barefoot for many months.” And cultural theorist Rinaldo Walcott (Canada) asks us to consider inheritances beyond white supremacist logics: “What might it mean to live a life, if we can’t risk desiring and working towards utopia?” As each alchemist considers the legacies of anticolonial struggle, the future of the planet, and the textures of Black and Indigenous life, their essays speak to each other in multiple ways, creating something startling and revelatory: a vision of the world as it is, and as it could be.
“One-and-a-Half” Interdural Transcavernous Pituitary Transposition/Rotation for Protection of Hypophyseal Portal System in Adult Peripheral Retroinfundibular Craniopharyngioma
Authors: Shen Ao , Yu Yang , Lyu Liang , Jiang Shu , Zhou Dongjie , Xu Jianguo , Zhou Peizhi
Published: March 2024

BACKGROUND AND OBJECTIVES:

Craniopharyngiomas originate from the pituitary stalk (PS) and extend along the pituitary-hypothalamic axis. Peripheral retroinfundibular craniopharyngiomas, particularly, may have worse surgery outcomes than other types. This study aims to investigate the advantage of using “one-and-a-half” interdural transcavernous pituitary transposition/rotation to dissect the tumor from the residual stalk and hypophyseal portal system for this subtype of craniopharyngioma.

METHODS:

From August 2018 to February 2023, patients with peripheral retroinfundibular craniopharyngioma underwent surgical treatment. We analyzed clinical information, surgical records, imaging, and examination findings. The surgical procedure, including “one-and-a-half” interdural transcavernous pituitary transposition and rotation, was explained. Postoperative follow-up included endocrinological tests, MRI examinations, and urination surveys.

RESULTS:

Among the 52 patients diagnosed with craniopharyngioma who underwent surgical treatment, 9 were classified as peripheral retroinfundibular craniopharyngioma, and they received “one-and-a-half” interdural transcavernous pituitary transposition and stalk rotation. In 6 cases, the residual PS and most of the hypophyseal portal system were preserved. Gross total resection was achieved in 5 patients and near total resection in 1 patient. One patient had a transection of the bilateral inferior hypophyseal arteries and 5 unilaterally. None experienced permanent diabetes insipidus, but varying degrees of anterior pituitary dysfunction postoperatively required hormone replacement therapy, which gradually decreased over time.

CONCLUSION:

The natural anatomic corridor, “one-and-a-half” interdural transcavernous pituitary transposition, and stalk rotation provide increased working space compared with intradural or extradural pituitary transposition. Simultaneously rotating the tumor and pituitary enables a specific attack angle for lesion dissection after the anteriorly displaced residual stalk is rotated laterally. This approach preserves the residual PS and hypophyseal portal system, avoiding complications of diabetes insipidus and hypopituitarism. In most cases, only one side of the inferior hypophyseal artery needs to be sacrificed, ensuring normal pituitary function.
CDX2 dose-dependently influences the gene regulatory network underlying human extraembryonic mesoderm development
Authors: Bulger Emily A. , McDevitt Todd C. , Bruneau Benoit G.
Published: March 2024

Loss of Cdx2 in vivo leads to stunted development of the allantois, an extraembryonic mesoderm-derived structure critical for nutrient delivery and waste removal in the early embryo. Here, we investigate how CDX2 dose-dependently influences the gene regulatory network underlying extraembryonic mesoderm development. By engineering human induced pluripotent stem cells (hiPSCs) consisting of wild-type (WT), heterozygous (CDX2-Het), and homozygous null CDX2 (CDX2-KO) genotypes, differentiating these cells in a 2D gastruloid model, and subjecting these cells to single-nucleus RNA and ATAC sequencing, we identify several pathways that are dose-dependently regulated by CDX2 including VEGF and non-canonical WNT. snATAC-seq reveals that CDX2-Het cells retain a WT-like chromatin accessibility profile, suggesting accessibility alone is not sufficient to drive this variability in gene expression. Because the loss of CDX2 or TBXT phenocopy one another in vivo, we compared differentially expressed genes in our CDX2-KO to those from TBXT-KO hiPSCs differentiated in an analogous experiment. This comparison identifies several communally misregulated genes that are critical for cytoskeletal integrity and tissue permeability. Together, these results clarify how CDX2 dose-dependently regulates gene expression in the extraembryonic mesoderm and reveal pathways that may underlie the defects in vascular development and allantoic elongation seen in vivo.
Physical Activity and Public Health for Adults: Is the Glass Mostly Empty or Half Full?
Authors: MATTHEWS CHARLES E. , SAINT-MAURICE PEDRO F. , BERRIGAN DAVID
Published: March 2024

Early observations that only a small proportion of U.S. adults were engaging in enough aerobic physical activity to provide substantial health benefit helped shape our public health messaging for physical activity. This messaging has consistently indicated that most adults should increase their activity levels. However, it has been difficult to accurately estimate the proportion of adults who engage in sufficient levels of aerobic activity in the population, with survey-based estimates ranging from 22% in 1994 to 54% in 2018 and widely differing estimates from device-based measures. Recent accelerometer-based studies of physical activity and mortality risk provide new evidence that at least 50% of U.S. adults engage in enough aerobic physical activity to be at low risk for premature mortality. We argue that this observation should lend greater confidence to our current survey-based surveillance estimates, which indicate that a large proportion of adults is physically active. This new insight may also provide clues that could further strengthen our public health messaging for physical activity by placing more emphasis on the maintenance of healthy activity levels throughout life and possibly by using descriptive social norms as an additional intervention element—while continuing current efforts to encourage the adoption of healthy activity levels for less active adults in the population.
Physiological and Metabolic Responses to Low-Volume Sprint Interval Exercises: Influence of Sprint Duration and Repetitions
Authors: YAMAGISHI TAKAKI , IWATA SOYA , OTSUKA SHUN , ICHINOSE HOSHIZORA , KAWAKAMI YASUO
Published: March 2024

Purpose

This study aimed to determine physiological and metabolic responses to two different sprint interval exercises (SIE) matched for total sprint duration and sprint–rest ratio.

Methods

After having measured peak oxygen uptake (V̇O2peak), 14 healthy males (27.1 ± 4.8 yr, 169.6 ± 6.0 cm, 64.5 ± 8.4 kg, V̇O2peak: 47.2 ± 7.7 mL·kg−1·min−1) performed four 10-s sprints with 80-s recovery (SIE10) and two 20-s sprints with 160-s recovery (SIE20) on different occasions in a counterbalanced crossover manner. Pulmonary V̇O2 and changes in tissue oxygenation index (∆TOI) at vastus lateralis (VL) and rectus femoris (RF) were measured during the SIE. Furthermore, T2-weighted magnetic resonance imaging was taken immediately before and after the SIE to determine the activation levels of VL, RF, vastus medialis, vastus intermedius, adductor magnus, biceps femoris long head, semitendinosus, and semimembranosus at 50% of right thigh length.

Results

In SIE10, increases in V̇O2 and ∆TOI at VL and RF plateaued after the second sprint, whereas session-averaged ∆TOI was greater in SIE20 than SIE10 in both muscles (VL: 20.9 ± 7.4 vs 14.2% ± 5.9%, RF: 22.8 ± 9.3 vs 12.9% ± 6.6%, P = 0.00). Although both SIE significantly increased T2 values in all eight muscles, those magnitudes were similar between the conditions (SIE10 vs SIE20: 5%–16% vs 8%–16%).

Conclusions

This study showed blunted responses of whole-body (V̇O2) and peripheral (∆TOI) oxidative responses with successive sprints (sprint 1 < sprints 2–4) in SIE10, suggesting that increasing sprint repetitions does not necessarily induce greater oxidative metabolism or stimulus. Moreover, greater peripheral oxygen extraction (∆TOI) was achieved with SIE20, whereas %changes of T2 indicates that the thigh muscles were similarly activated between the SIE conditions.
Determinants of Change in Physical Activity in Children during the Transition from Elementary to High School
Authors: PATE RUSSELL R. , DOWDA MARSHA , DISHMAN ROD K. , SAUNDERS RUTH P. , CORDAN KERRY L. , SHULL EMILY R. , BUCKO AGNES G. , COLABIANCHI NATALIE
Published: March 2024

Introduction

Effective public health interventions targeting factors that influence physical activity are urgently needed to reduce the age-related decline in physical activity in youth. The purpose of this study was to identify associations between physical activity and a set of potential influences on physical activity in children as they transition from elementary to high school.

Methods

Participants were 951 children from South Carolina school districts who completed outcome and independent variable measures on at least two time points from the 5th to 11th grades in 2010–2017. The primary outcome variable was physical activity, measured by accelerometry. Independent variables included a comprehensive set of variables in the child, parent/home, school, and community domains. Children, parents and school administrators, and staff completed questionnaires to assess psychosocial and home, school, and neighborhood environmental influences. Growth curve analyses identified independent variables associated with physical activity over time, either as a main effect or as an interaction with age.

Results

As main effects, self-efficacy, self-schema, sport participation, weekday outdoor hours, importance of child participating in sports and physical activity, safe to play outside, and Physical Activity Resource Assessment weighted score were positively associated with physical activity. The associations between physical activity and enjoyment motivation, appearance motivation, weekend outdoor time, and home equipment exhibited significant interactions with age. Enjoyment motivation influenced physical activity during the earlier years, whereas the remaining three variables influenced physical activity in the later years.

Conclusions

Interventions should target multiple domains of influences that may vary by age.
The Implications of Great Power Politics in the Decade Long Syrian Civil War
Authors: İleri Kasım
Published: March 2024

This research analyzes the implications US and Russian involvement has had as two great powers in the Syrian civil war for international relations in the Middle East as well as for the relations between Washington and Moscow. Using a structural realist approach, this study suggests that the actions of both the US and Russia have mostly been defined by geopolitical status-quo concerns. As a result, they have preferred that their great power play be contained in Syria. As key findings, this study puts forward that the US-Russia showdown in Syria has prolonged the destruction and shaken US alliances in the region while allowing Iran as a key US adversary in the region to extend its influence deep into the region under cover of Russia. Furthermore, contrary to their broader escalatory security policies, Russia and the US have adopted containment approaches and avoided direct confrontation using Cold War tools.
Mediated narratives in the arrival laandscape
Authors: Ουρεϊλίδου Ελένη
Published: March 2024

Αντικείμενο μελέτης της διδακτορικής διατριβής είναι το αναδυόμενο μετα-ψηφιακό τοπίο και η εισαγωγή καινοτόμων ψηφιακών εργαλείων στην συλλογική διαμόρφωση των αστικών υπαίθριων χώρων. Η έρευνα εστιάζει σε πρόσφατες “από τα κάτω προς τα πάνω” πρωτοβουλίες, οι οποίες ενισχύουν την κοινωνική ανθεκτικότητα των δημόσιων ελεύθερων χώρων. Σκοπός της έρευνας είναι να μελετηθεί ο τρόπος με τον οποίο τα ψηφιακά εργαλεία συνδεσιμότητας εφαρμόζονται στο αστικό περιβάλλον, κατά πόσο ανταποκρίνονται στις προκλήσεις των πόλεων Άφιξης νέων πληθυσμιακών ομάδων, προτείνοντας σενάρια ενσωμάτωσης τους σε επίπεδο κοινωνικό, οικονομικό και πολιτιστικό. Στο θεωρητικό υπόβαθρο της έρευνας, αναλύονται οι όροι της Αστικής και Κοινωνικής Ανθεκτικότητας, του Τοπίου των Μεγάλων Δεδομένων, και της ρητορικής των Έξυπνων Πόλεων. Η υπόθεση εργασίας εστιάζει στην χρήση των ψηφιακών μέσων με σκοπό την διαμεσολαβημένη διήγηση στιγμιότυπων της πόλης από τους χρήστες. Η μεθοδολογία περιλαμβάνει την κειμενική ανάλυση ψηφιακών τεχνουργημάτων για την ανάλυση του τοπίου της άφιξης, προτείνοντας προγραμματιστικά εργαλεία για την επίλυση αστικών παθογενειών. Εν τέλει, τα αποτελέσματα της διδακτορικής διατριβής τροφοδοτούν μελλοντική έρευνα πάνω στα ψηφιακά εργαλεία και την άρση του αποκλεισμού κοινωνικών ομάδων από τη χρήση του δημόσιου χώρου, εντείνοντας την δημοκρατική διαχείριση του αστικού περιβάλλοντος.
High throughput biological sequence analysis using machine learning-based integrative pipeline for extracting functional annotation and visualization
Authors: Al Amin Md , Naznin Feroza , Yeasmin Most Nilufa , Sarkar Md Sumon , Misor Mia Md , Chowdhury Abdullahi , Islam Md Zahidul
Published: March 2024

The Differential Gene Expression (DGE) approach to find out the expressed genes relies on measures such as log-fold change and adjusted p-values. Although fold change is commonly employed in gene expression studies, especially in microarray and RNA sequencing experiments to quantify alterations in a gene’s expression level, a limitation and potential hazard of relying on fold change in this context is its inherent bias. As a consequence, it might incorrectly categorize genes that have significant differences but minor ratios, resulting in poor detection of mutations in genes with high expression levels. In contrast, machine learning offers a more comprehensive view, adept at capturing the non-linear complexities of gene expression data and providing robustness against noise that inspired us to utilize machine learning models to explore differential gene expression based on feature importance in Type 2 Diabetes (T2D), a significant global health concern, in this study. Moreover, we validated biomarkers based on our findings expressed genes with previous studies to ensure the effectiveness of our ML models in this work which led us to go through to analysis pathways, gene ontologies, protein-protein interactions, transcription factors, miRNAs, and drug predictions to deal with T2D. This study aims to consider the machine learning technique as a good way to know about expressed genes profoundly not relying on the DGE approach, and to control or reduce the risk of T2D patients by helping drug developer researchers.
Optimal Consolidation of Polling Locations
Authors: Schmidt Adam P. , Buell Duncan , Albert Laura A.
Published: March 2024

Problem definition: Many logistical and financial challenges of facilitating an election lead election officials to consolidate polling locations. However, determining when it is appropriate to consolidate polling locations and how to consolidate polling locations, if necessary, is a difficult and high-stakes decision that influences voter participation. Methodology/results: We formalize the set of constraints and criteria that election officials should follow as the polling location consolidation problem (PLCP), which is formulated as an integer programming model. The PLCP simultaneously selects which polling locations will be used in the upcoming election, reassigns voter precincts to polling locations, and allocates critical resources to the selected polling locations. The PLCP minimizes the increased distance that voters must travel to their updated polling location. Because empirical research also demonstrates the importance of reducing the voters’ wait times, we require that most voters do not wait longer than a prespecified limit, such as 30 minutes, using a chance constraint. We prove that identifying a feasible solution to PLCP is NP-complete, which demonstrates the difficulty in making consolidation decisions, as well as the importance of optimization for this problem. Managerial implications: This paper introduces a structured and transparent approach to support election officials in making informed, data-driven decisions regarding how and when to consolidate polling locations that minimally impact voters and encourage voter participation. The approach could be used to develop preapproved contingency plans that could be employed if there are major disruptions to an election.

Supplemental Material: The online supplement is available at https://doi.org/10.1287/msom.2022.0497 .