bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intermittent or Continuous Panitumumab Plus Fluorouracil, Leucovorin, and Irinotecan for First-Line Treatment of
RAS
and
BRAF
Wild-Type Metastatic Colorectal Cancer: The IMPROVE Trial
Authors: Avallone Antonio , Giuliani Francesco , De Stefano Alfonso , Santabarbara Giuseppe , Nasti Guglielmo , Montesarchio Vincenzo , Rosati Gerardo , Cassata Antonino , Leo Silvana , Romano Carmela , Tamburini Emiliano , Silvestro Lucrezia , Lotesoriere Claudio , Nappi Anna , Santini Daniele , Petrillo Antonella , Colombo Alfredo , Febbraro Antonio , Leone Alessandra , Mannavola Francesco , Laterza Maria Maddalena , Izzo Francesco , Sobrero Alberto , Delrio Paolo , Giannarelli Diana , Budillon Alfredo 
Published: November 2024

PURPOSE

To investigate whether intermittent treatment after an induction phase of first-line schedule of fluorouracil, leucovorin, and irinotecan (FOLFIRI) plus panitumumab (PAN) prevents or delays the onset of resistance and improves safety and compliance with treatment in patients with unresectable
RAS
/
BRAF
wild-type (wt) metastatic colorectal cancer (mCRC).

PATIENTS AND METHODS

IMPROVE (ClinicalTrials.gov identifier:
NCT04425239
) was an open-label, multicenter, randomized phase II noncomparative trial. Patients with unresectable
RAS
/
BRAF
wt mCRC were randomly assigned (1:1) to receive FOLFIRI plus PAN continuously until progression (arm A) or intermittently, with treatment-free intervals (arm B) until progression on treatment, toxicity, or death. The primary end point was progression-free survival on treatment (PFSot) at 12 months. Assuming a null hypothesis of median PFSot time ≤7 months and target PFSot ≥10 months, 65 patients per arm were needed to achieve 80% power and 10% type I error, according to the binomial test.

RESULTS
Between May 2018 and June 2021, 69 patients were randomly assigned to arm A and 68 to arm B. The median number of treatment cycles was 13 in arm A and 16 in arm B. At a median follow-up of 43.2 months (IQR, 35.0-50.5), median PFSot was 11.2 and 17.5 months with 12-month PFSot rates of 45.7% and 58.5%, for arms A and B, respectively. The overall response rates were 68.1% and 61.2%, and median overall survival rates were 36.3 and 35.1 months in arms A and B, respectively. The overall rate of grade >2 skin PAN-related adverse events was 30.3% in arm A and 17.9% in arm B.

CONCLUSION
Intermittent FOLFIRI plus PAN after the induction phase was feasible, and the primary end point was met with reduced toxicity while allowing patients more time off treatment.
Disordered Electron Transfer: New Forms of Defective Steroidogenesis and Mitochondriopathy
Authors: Miller Walter L , Pandey Amit V , Flück Christa E 
Published: November 2024

Abstract
Most disorders of steroidogenesis, such as forms of congenital adrenal hyperplasia (CAH) are caused by mutations in genes encoding the steroidogenic enzymes and are often recognized clinically by cortisol deficiency, hyper- or hypo-androgenism, and/or altered mineralocorticoid function. Most steroidogenic enzymes are forms of cytochrome P450. Most P450s, including several steroidogenic enzymes, are microsomal, requiring electron donation by P450 oxidoreductase (POR); however, several steroidogenic enzymes are mitochondrial P450s, requiring electron donation via ferredoxin reductase (FDXR) and ferredoxin (FDX). POR deficiency is a rare but well-described form of CAH characterized by impaired activity of 21-hydroxylase (P450c21, CYP21A2) and 17-hydroxylase/17,20-lyase (P450c17, CYP17A1); more severely affected individuals also have the Antley-Bixler skeletal malformation syndrome and disordered genital development in both sexes, and hence is easily recognized. The 17,20-lyase activity of P450c17 requires both POR and cytochrome b5 (b5), which promote electron transfer. Mutations of POR, b5, or P450c17 can cause selective 17,20-lyase deficiency. In addition to providing electrons to mitochondrial P450s, FDX, and FDXR are required for the synthesis of iron-sulfur clusters, which are used by many enzymes. Recent work has identified FDXR mutations in patients with visual impairment, optic atrophy, neuropathic hearing loss, and developmental delay, resembling the global neurologic disorders seen with mitochondrial diseases. Many of these patients have had life-threatening events or deadly infections, often without an apparent triggering event. Adrenal insufficiency has been predicted in such individuals but has only been documented recently. Neurologists, neonatologists, and geneticists should seek endocrine assistance in evaluating and treating patients with mutations in FDXR.
Ephemeral Diabetes After COVID-19 Vaccination
Authors: Mänd Sarah-Ålivia , Sjöholm Åke 
Published: November 2024

Abstract
We report a case of new-onset, nonautoimmune, nonketotic, and noninsulinopenic type 2-like diabetes in a previously normoglycemic middle-aged man debuting after vaccination against COVID-19. This was not a mild or short-lived glucose intolerance, but severe and long-standing hyperglycemia with a high glycated hemoglobin level. However, the course of the diabetes was highly atypical and surprising in that it spontaneously disappeared after a few months and did not recur despite the patient being off all antidiabetic drugs for several months and without any changes in body weight or lifestyle. The mechanisms by which severe diabetes unfolded and later remitted in this patient remain elusive. Nonetheless, and notwithstanding whether or not there was a cause-and-effect relation between the vaccinations and his diabetes, the highly atypical course of spontaneously remitting nonautoimmune diabetes lends itself to mechanistic efforts aimed at understanding the biology and pathophysiology of insulin-producing β cells in health and disease. This case report should not be construed as vaccine skepticism or deter anyone, especially with diabetes/obesity, from vaccination against COVID-19. However, it calls for increased vigilance among health care providers for unusual and unexpected metabolic effects of COVID-19 and its vaccines.
Relationship Between 1,5 Anhydroglucitol, Glycemia, and Breastfeeding During Pregnancy and Postpartum: A Pilot Study
Authors: Soffer Marti D , James Kaitlyn E , Callahan Michael , Rosenberg Emily A , Barth William H , Powe Camille E 
Published: November 2024

Abstract

Background
Assessments for hyperglycemia are vital to pregnancy and postpartum (PP) care, but gold-standard oral glucose tolerance tests (OGTTs) are burdensome. We examined changes in 1,5 anhydroglucitol (1,5AG) levels during gestation and PP and assessed for associations with other measures of glycemia.

Study Design
Pregnant participants (n = 50) in the Study of Pregnancy Regulation of Insulin and Glucose cohort underwent OGTTs at a mean of 13 weeks ([visit 1 (V1)] and 26 weeks [visit 2 (V2)] of gestation and PP. Nonpregnant controls had a single OGTT. 1,5AG was measured using frozen plasma samples. Changes in 1,5AG across pregnancy were assessed with longitudinal mixed effects linear models. We assessed relationships between 1,5AG and glycemia at each timepoint using Spearman correlations and linear regression models. To determine the relationship of 1,5AG with breastfeeding (BF) status, stratified analyses were performed.

Results
1,5AG decreased from V1 to V2 (β = −3.6 μg/mL, P &lt; .001) and remained low PP compared to V1 (β = −1.4 μg/mL, P = .018). Comparisons between pregnant/PP and nonpregnant participants revealed lower 1,5AG values at all timepoints (V1 β = −9.9μg/mL, P &lt; .001; V2 β = −14.0 μg/mL, P &lt; .001, PP β = −11.4μg/mL, P &lt; .001). There was no association between 1,5AG and glycemia. Compared to those exclusively feeding formula, 1,5AG levels were significantly lower in exclusively BF women (β = −8.8 μg/mL, P &lt; .001) and intermediate in women feeding both breastmilk and formula (β = −6.1μg/mL, P &lt; .001), independent of glycemia.

Conclusion
1,5AG decreases during gestation and remains low PP. Breastfeeding is associated with lower 1,5AG levels, indicating plausible excretion into breastmilk. 1,5AG is unlikely to be useful in assessing glycemia in pregnant or PP women.
“I Authored This Book in the Absence of My Slave”: Enslaved East Africans and the Production of Occult Knowledge across the Omani Empire
Authors: AlMaazmi Ahmed Yaqoub 
Published: November 2024

Abstract
What role did enslaved East Africans play in producing and transmitting the occult sciences between East Africa and Oman? This article explores the relationship between enslaved East Africans and the occult sciences in the works of Nāṣir bin Abī Nabhān (1778–1846), a jurist and practitioner of the occult sciences who lived between Oman and East Africa. It argues that enslaved East Africans were instrumental in producing and disseminating valuable occult knowledge. The analysis informs how occult knowledge operated and circulated between the Arabian and African coasts, animated in occultist idioms, and was written in Arabic and Swahili. Moreover, it explores how East African and Omani actors articulated occultist knowledge by paying attention to the interlinkages between power dynamics and knowledge hierarchies during the expansion of the Bu Saidi Empire in the nineteenth century. This study explores uncharted waters in a transoceanic sphere by tracing translation processes and non-European imperial knowledge production in the Indian Ocean world.
Beyond genomic studies of congenital heart defects through systematic modelling and phenotyping
Authors: Henderson Deborah J. , Alqahtani Ahlam , Chaudhry Bill , Cook Andrew , Eley Lorraine , Houyel Lucile , Hughes Marina , Keavney Bernard , de la Pompa José Luis , Sled John , Spielmann Nadine , Teboul Lydia , Zaffran Stephane , Mill Pleasantine , Liu Karen J. 
Published: November 2024

ABSTRACT
Congenital heart defects (CHDs), the most common congenital anomalies, are considered to have a significant genetic component. However, despite considerable efforts to identify pathogenic genes in patients with CHDs, few gene variants have been proven as causal. The complexity of the genetic architecture underlying human CHDs likely contributes to this poor genetic discovery rate. However, several other factors are likely to contribute. For example, the level of patient phenotyping required for clinical care may be insufficient for research studies focused on mechanistic discovery. Although several hundred mouse gene knockouts have been described with CHDs, these are generally not phenotyped and described in the same way as CHDs in patients, and thus are not readily comparable. Moreover, most patients with CHDs carry variants of uncertain significance of crucial cardiac genes, further complicating comparisons between humans and mouse mutants. In spite of major advances in cardiac developmental biology over the past 25 years, these advances have not been well communicated to geneticists and cardiologists. As a consequence, the latest data from developmental biology are not always used in the design and interpretation of studies aimed at discovering the genetic causes of CHDs. In this Special Article, while considering other in vitro and in vivo models, we create a coherent framework for accurately modelling and phenotyping human CHDs in mice, thereby enhancing the translation of genetic and genomic studies into the causes of CHDs in patients.
Effects of Resistance Training on Muscular Adaptations and Inflammatory Markers in Overweight and Obese Men
Authors: BAGHERI NAVID , BAGHERI REZA , MESINOVIC JAKUB , GHOBADI HAMID , SCOTT DAVID , KARGARFARD MEHDI , DUTHEIL FRED 
Published: November 2024

ABSTRACT

Purpose
Obesity may blunt exercise responsiveness to improve muscular adaptations. The effect of resistance training (RT) targeting different body regions on muscle and inflammatory markers is unclear. This study aimed to investigate the impact of upper (upper body exercises), lower (lower body exercises), or combined (upper body + lower body exercises) RT on muscle and inflammatory markers, body composition, and performance in overweight and obese men.

Methods
Sixty overweight and obese men (age, 31 ± 4 yr) were randomly assigned to one of four groups: upper-body RT (UB; n = 15), lower-body RT (LB; n = 15), combined RT (UB + LB; n = 15), or control (C; n = 15). The training protocol consisted of three exercise sessions per week for 12 wk. Blood samples for measuring serum markers (follistatin, myostatin, C-reactive protein (CRP), adiponectin, tumor necrosis factor α (TNF-α), and irisin) were obtained at baseline and 48 h after the final training session. Fat mass (FM), body fat percentage, skeletal muscle mass (SMM), and fat-free mass were measured using bioelectrical impedance analysis (InBody 720).

Results
SMM, fat-free mass, UB and LB strength and power, follistatin, follistatin/myostatin ratio, adiponectin, and irisin significantly increased, whereas FM, body fat percentage, myostatin, CRP, and TNF-α significantly reduced from pre- to post-training in all training groups (P < 0.05). Changes in LB muscle power (r = 0.558), both UB (r = 0.518) and LB (r = 0.419) muscle strength, and follistatin (r = 0.545) had moderate positive relationships with ΔSMM, whereas changes in myostatin (r = −0.585) had a moderate negative relationship with ΔSMM. Also, changes in myostatin (r = 0.825) and CRP (r = 0.715) had a strong positive relationship with ΔFM, whereas TNF-α (r = 0.467) had a moderate positive relationship with ΔFM. Follistatin (r = −0.789) and adiponectin (r = −0.713) had a strong negative relationship with ΔFM, whereas irisin (r = −0.426) had a moderate negative relationship with ΔFM.

Conclusions
Combined RT elicits the greatest increases in follistatin, follistatin/myostatin ratio, and adiponectin, and decreases in myostatin and CRP compared with other training groups in overweight and obese men. However, systemic improvements may be achieved through performing UB or LB RT alone.
Algorithmic Audits in Sports Medicine: An Examination of the SpartaScience TM Force Plate System
Authors: Butler Cody R , Scott W. Casan , Hando Ben , Angadi Siddhartha S. 
Published: November 2024

ABSTRACT

Introduction
Force plate systems are increasingly utilized in the armed forces that claim to identify individuals at risk of musculoskeletal injury. However, factors influencing injury risk scores from a force plate system (SpartaScienceTM), and the effects of experimental perturbations on these scores, remain unclear.

Methods
Healthy males (n = 823; 22.7 ± 3.9 years) performed a countermovement jump (CMJ) on SpartaScienceTM force plates. Multiple regression analysis was used to identify predictors of the system’s proprietary Musculoskeletal (MSK) Health score which were then experimentally perturbed. Twelve males (30.9 ± 4.3 years) participated in a test-retest reliability study, performing three standard CMJs and one experimentally manipulated jump (50% effort) due to the observed relationship between the MSK Health score, vertical jump height and body weight.

Results
The MSK Health score was negatively correlated with vertical jump height and positively with body weight (R2 = 0.59, p < 0.001). Each inch increase in jump height decreased the MSK Health score by an average of 1.27 units (95% CI: 1.17, 1.36), while each pound of body weight increased it by 0.12 units (95% CI: 0.11, 0.13). Notably, 83% of participants in the reliability study improved their MSK Health score on the 50% effort jump.

Conclusions
The study revealed atypical relationships between MSK Health scores, vertical jump height, and body weight, with vertical jump height playing a majority role in predicting the principal output (MSK Health score). Findings indicated a higher injury risk with greater jump height but a lower risk with increased body weight. Additionally, MSK Health scores paradoxically improved with lower effort (i.e. lower vertical jump height) which highlights the dangers of using undisclosed and unvetted algorithms for the prediction of health outcomes.
Impact of Temporary Store Closures on Online Sales: Evidence from a Natural Experiment
Authors: Gürlek Ragıp , KC Diwas Singh , Letizia Paolo 
Published: November 2024

Problem definition: This paper examines the impact of retail store closures on omnichannel sales and consumer shopping behavior in the context of the coronavirus disease 2019 pandemic. To explain the likelihood of store closure, we develop a novel instrumental variable motivated by varying geopolitical responses across the United States to the pandemic. Methodology/results: Using data from a luxury fashion retailer, we find that when a store is closed, the volume of online orders originating from its location increases by 24%. Furthermore, when the retailer closes 10% of its stores, the omnichannel total sales (offline + online) decrease by 5.5%. Notably, our findings indicate that the online channel enables the retailer to recover 11% of offline sales that would have otherwise been lost because of store closures. We also show that compared with existing e-shoppers, new e-shoppers are more likely to order popular product models in an effort to mitigate the heightened mismatch risk associated with online transactions. For new e-shoppers, the likelihood of ordering a popular model stands at 70%, whereas it is 45% for existing online consumers. Additionally, the conservative behavior of favoring popular models reduces the likelihood of returns by new e-shoppers. Managerial implications: Even for luxury apparel, which is often associated with in-store purchases requiring “touch and feel” and customer tryout, the option to purchase online proves immensely valuable. The tendency of new e-shoppers to limit product mismatch risk by choosing popular products may create an opportunity for retailers to strategically target these inexperienced online customers with advertisements, product promotions, or virtual fitting rooms, all geared toward reducing online shopping risk of product mismatch. Supplemental Material: The online appendix is available at https://doi.org/10.1287/msom.2022.0527 .
TRANSITIONING FROM EMPIRIC TO CULTURE-SPECIFIC ANTIBIOTIC THERAPY FOLLOWING SURGICAL DEBRIDEMENT IN BONE AND PERIPROSTHETIC JOINT INFECTION: HOW LONG DO WE NEED TO WAIT?
Authors: Elder Ashley , Wijendra Asanka , Hotchen Andrew , Wangrangsimakul Tri , Young Bernadette , Barrett Lucinda , Ferguson Jamie 
Published: November 2024

AimAn instrumented blood culture system automatically flags when growth within the culture medium has been detected (‘work in progress’), and subsequently when the organism has been identified.We explore using this data to switch patients to oral therapy within 72 hours post-surgery, reducing costs and improving antimicrobial stewardship.MethodThis retrospective review focused on clinically significant culture-positive bone and joint infections over a 5-month period in 2022. Two cohorts were defined as either having positive intraoperative microbiology at <72 hours or at ≥72 hours.Results150 patients were included. 133/150(88%) exhibited microbial growth <72hours. Of these, 98/133(74%) had all organisms identified <72-hours, and 34/133(26%) had additional organisms ≥72 hours. 19/151(12%) patients had their first positive cultures ≥72hrs from sampling.The most common isolates identified within 72 hours were S. aureus(30%), Enterobacteriaceae (26%), and Coagulase-negative Staphylococcus (CoNS)(19%). If no growth was observed by 48 hours, there was a 69.6% probability that subsequent growth wouldn't occur; this probability increases to 81.9% by 72 hours, 88.7% by 96 hours, 91.0% by 120 hours, and 95.0% by 144 hours (see figure 1). The most common isolates identified ≥72 hours were CoNS(28%), Cutibacterium acnes(16%) and S. aureus(12%). Assessing oral antibiotic regimes for isolates identified after 72 hours demonstrated that linezolid would cover isolates from 96% of patients, tetracyclines 92% of patients, clindamycin 85% of patients, and ciprofloxacin and rifampicin would cover 80% of patients. Vancomycin and meropenem, our standard empirical therapy, gave the best cover at 96% of patients.ConclusionsThis study suggests there is sufficient microbiological information at 72 hours for most patients to allow transition to a targeted regimen. If there has been no detection of growth when using an instrumented blood culture system by 72 hours, it is likely that there will be no growth.For any tables or figures, please contact the authors directly.
Linear-optical four-dimensional Bell state measurement for superdense coding assisted by polarization entanglement
Authors: Zeng Zhi 
Published: November 2024

With the assistance of auxiliary two-dimensional polarization entanglement, we theoretically present an efficient Bell state measurement (BSM) method for photonic four-dimensional entanglement in the path degree of freedom, in which just simple linear optical elements and common single-photon detectors are utilized. With this approach, the 16 mutually orthogonal four-dimensional path Bell states can be classified into eight distinguishable groups, which allows the transmission of 3 bits of classical information by just sending one photon in our quantum superdense coding protocol. Compared with previous quantum dense coding protocols that are also based on linear-optical BSM, our protocol has certain advantages and will be useful for other quantum communication protocols based on high-dimensional entanglement.
Just Independence Wars and the October 7th Massacre
Authors: Benbaji Yitzhak 
Published: November 2024

Abstract
This essay explores a view held by many critics of Israel, which posits that the October 7th massacre is a war crime that is part of a just war of independence, fought by Palestinians against Israel for over a century. Raef Zreik recently presented such a view in these pages. However, this essay argues that a proper understanding of traditional just war theory renders this view false. Even if Zionism is considered a colonial wrong, Palestinians did not have a just cause for war against Zionism until after the Six-Day War in 1967 and perhaps later. Furthermore, the essay contends that the massacre is not a part of this war, as Hamas lacks the moral power to represent the Palestinian people and to fight in their name.
Précis of Philosophizing the Indefensible
Authors: Nili Shmuel 
Published: November 2024

Abstract
This book asks what distinctive contributions political philosophers might make when reflecting on obvious moral failures in public policy. I defend a particular kind of contribution: I argue that political philosophers can and should craft ‘strategic’ arguments for public policy reforms, showing how morally urgent reforms can be grounded, for the sake of discussion, even in problematic premises associated with their opponents. The book’s opening chapter provides a general defense of this approach, situating it within a broader conception of political philosophy’s social responsibilities. Subsequent chapters then apply strategic theorizing to a set of diverse policy issues. These range from the abortion debate and financial regulation in the United States, through controversies surrounding the participation of Arab parties in Israel’s political process, to global issues, such as commercial ties with oil-rich dictatorships, and the bearing of such ties on global climate change.