bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Systematic Review and Pooled Analysis of Hypothesized versus Observed Effect Sizes in Early Phase Cancer Prevention Clinical Trials
Authors: Eickhoff Jens , Zaborek Jen , Chen Guanhua , Sahasrabuddhe Vikrant V. , Ford Leslie G. , Szabo Eva , Kim KyungMann 
Published: June 2023

Abstract

Early phase cancer prevention trials are designed to demonstrate safety, tolerability, feasibility, and signals of efficacy of preventive agents. Yet it is often observed that many trials fail to detect intervention effects. We conducted a systematic review and pooled analyses of recently completed early phase chemoprevention trials to gain in depth insight on the failure of detecting efficacy signals by comparing hypothesized effect sizes to the corresponding observed effect sizes.
Single- or multi-arm efficacy chemoprevention trials conducted under the phase 0/I/II Cancer Prevention Clinical Trials Program of the Division of Cancer Prevention, NCI between 2003 and 2019 were evaluated. A total of 59 chemoprevention trials were reviewed. Twenty-four studies were efficacy or biomarker trials with complete information on hypothesized and observed effect sizes and included in this analysis. The majority of the trials (n = 18) were multi-arm randomized studies of which 15 trials were blinded. The pooled estimate of the observed to hypothesized effect size ratio was 0.57 (95% confidence interval: 0.42–0.73, P &lt; 0.001) based on a random-effects model. There were no significant differences detected in the ratio of observed to hypothesized effect sizes when conducting various subgroup analyses.
The results demonstrate that the majority of early phase cancer chemoprevention trials have substantially smaller observed effect sizes than hypothesized effect sizes. Sample size calculations for early phase chemoprevention trials need to balance the potential detectable effect sizes with realistic and cost-effective accrual of study populations, thereby, detecting only intervention effects large enough to justify subsequent large-scale confirmatory trials.

Prevention Relevance:
The results of this systematic review and pooled analyses demonstrate that for early chemoprevention trials, there are substantial differences between hypothesized and observed effect sizes, regardless of study characteristics. The conduct of early phase chemoprevention trial requires careful planning of study design, primary endpoint, and sample size determination.
Mitochondrial-Encoded Complex I Impairment Induces a Targetable Dependency on Aerobic Fermentation in Hürthle Cell Carcinoma of the Thyroid
Authors: Frank Anderson R. , Li Vicky , Shelton Spencer D. , Kim Jiwoong , Stott Gordon M. , Neckers Leonard M. , Xie Yang , Williams Noelle S. , Mishra Prashant , McFadden David G. 
Published: June 2023

Abstract

A metabolic hallmark of cancer identified by Warburg is the increased consumption of glucose and secretion of lactate, even in the presence of oxygen. Although many tumors exhibit increased glycolytic activity, most forms of cancer rely on mitochondrial respiration for tumor growth. We report here that Hürthle cell carcinoma of the thyroid (HTC) models harboring mitochondrial DNA-encoded defects in complex I of the mitochondrial electron transport chain exhibit impaired respiration and alterations in glucose metabolism. CRISPR–Cas9 pooled screening identified glycolytic enzymes as selectively essential in complex I–mutant HTC cells. We demonstrate in cultured cells and a patient-derived xenograft model that small-molecule inhibitors of lactate dehydrogenase selectively induce an ATP crisis and cell death in HTC. This work demonstrates that complex I loss exposes fermentation as a therapeutic target in HTC and has implications for other tumors bearing mutations that irreversibly damage mitochondrial respiration.

Significance:
HTC is enriched in somatic mtDNA mutations predicted to affect complex I of the electron transport chain (ETC). We demonstrate that these mutations impair respiration and induce a therapeutically tractable reliance on aerobic fermentation for cell survival. This work provides a rationale for targeting fermentation in cancers harboring irreversible genetically encoded ETC defects.
See related article by Gopal et al., p. 1904.
This article is highlighted in the In This Issue feature, p. 1749
Сучасні підходи до діагностики негативного впливу незнімного зубного протезування на тканини пародонта та його профілактики (огляд літератури)
Authors: Бєліков О. Б. , Рощук О. І. , Гавалешко В. П. , Караван Я. Р. 
Published: June 2023

Резюме. У статті представлено науковий огляд літератури про об’єктивізацію впливу незнімних зубних протезів на тканини пародонта, особливо виготовлених із сплавів неблагородних металів.
Мета дослідження – проаналізувати дані наукових літературних джерел стосовно проблеми негативного впливу конструкційних матеріалів незнімних зубних протезів на тканини пародонта.
Матеріали і методи. Використано бібліосемантичний метод, щоби з’ясувати стан проблеми, проаналізувати результати попередніх наукових досліджень на основі джерел літератури та електронних ресурсів.
Результати досліджень та їх обговорення. У літературі описано участь процесів пероксидного окиснення ліпідів та білків у патогенезі захворювань тканин пародонта у хворих із незнімними зубними протезами, а також заходи захисту тканин пародонта від негативного впливу незнімних металевих зубних протезів, зокрема антиоксидантну терапію. Подано варіанти раціонального зубного протезування пацієнтів із захворюваннями тканин пародонта і застосуванням біоінертних конструкційних матеріалів.
Висновки. Ортопедичне лікування пацієнтів із захворюваннями тканин пародонта необхідно проводити після провокаційних тестів, щоби вчасно виявити непереносимість металевих включень, або застосовувати сучасні безметалеві керамічні конструкції на основі діоксиду цирконію.
Підвищення безпеки операційних втручань у вагітних із первинним хронічним захворюванням вен в умовах гіпотензивного синдрому
Authors: Антонюк-Кисіль В. М. , Дзюбановський І. Я. , Єнікеєва В. М. , Лічнер С. І. , Липний В. М. , Дрозд В. В. 
Published: June 2023

У статті наведено огляд сучасних міжнародних настанов та дані останніх джерел літератури як вітчизняних, так і закордонних авторів синдрому нижньої порожнистої вени у вагітних.
Наведені короткі відомості з анатомії, патофізіології, діагностики, прогнозування та запобігання і безмедикаментозного лікування синдрому нижньої порожнистої вени у вагітних.
Оцінено можливості передбачення в запобіганні синдрому нижньої порожнистої вени у вагітних у реальній клінічній практиці з врахуванням сучасних міжнародних настанов для підвищення позитивних результатів планового хірургічного втручання під місцевим знеболенням внаслідок первинного хронічного захворювання вен у вагітних у закладах охорони здоров’я України.
НАПРЯМИ ВДОСКОНАЛЕННЯ ВИКЛАДАННЯ ПЕДІАТРІЇ В ЗАКЛАДАХ ВИЩОЇ ОСВІТИ
Authors: Волосовець О. П. , Уліщенко В. В. , Грищенко Н. В. , Ковальчук О. Л. , Купкіна А. В. , Каруліна Ю. В. , Ємець О. В. , Хоменко В. Є. , Салтанова С. Д. 
Published: June 2023

Анотація. Вимоги, зумовлені реформуванням системи медичної освіти у зв’язку зі вступом нашої країни до єдиного європейського і світового простору, і водночас умови війни та пандемії визначають підвищену потребу пошуку ефективних методів підготовки майбутніх фахівців. Дана робота присвячена аналізу результатів анонімного опитування студентів 6 курсу медичного факультету, спеціальність 222 «Медицина», які завершили дисципліну «Педіатрія» на кафедрі педіатрії № 2 Національного медичного університету імені О. О. Богомольця, щодо оцінки засвоєння дисципліни, форм і методів навчання. На думку студентів, змішана форма навчання є найбільш ефективною системою організації навчального процесу при вивченні педіатрії на сучасному етапі. Аналіз результатів анкетування виявив певні труднощі у студентів при вивченні окремих розділів педіатрії (кардіології, нефрології), опануванні надання екстреної допомоги дітям при деяких невідкладних станах, навичок маніпуляцій та інтерпретації результатів інструментальних методів дослідження. Серед ймовірних причин труднощів під час вивчення педіатрії переважна більшість студентів зазначила брак часу для вивчення теми, недостатній рівень засвоєння знань при вивченні попередніх дисциплін та недостатню кількість аудиторних занять. Найбільш ефективним методом навчання переважна більшість студентів вважає вирішення та обговорення клінічних кейсів. Водночас самостійне вирішення клінічних завдань є складним для значної кількості студентів. Збільшення застосування можливостей цифрових технологій у навчальному процесі, посилення інтегративних міждисциплінарних зв’язків та пререквізитів, надання можливості студентам додаткових тренінгів з опанування маніпуляцій є потужними інструментами підвищення ефективності засвоєння педіатрії.
Repetitive Antigen Responses of LDL-Reactive CD4+ T Cells Induce Tr1 Cell–Mediated Immune Tolerance
Authors: Mailer Reiner K. , Konrath Sandra , Zhan Lydia , Thode Hanna , Beerens Manu , Frye Maike , Ketelhuth Daniel F.J. , Renné Thomas , Hansson Göran K. 
Published: June 2023

BACKGROUND:
Inflammation triggered by the deposition of LDL (low-density lipoprotein) in the arterial wall leads to the development of atherosclerosis. Regulatory T (Treg) cells inhibit vascular inflammation through the induction of immune tolerance toward LDL-related antigens. However, tolerogenic mechanisms that promote the generation of LDL-specific Treg cells in vivo remain unclear.

METHODS:
We identified LDL-specific T cells by activation-induced marker expression and analyzed expression profiles and suppressive functions of TCR (T-cell antigen receptor)-transgenic T cells upon repetitive transfer into antigen-transgenic mice via flow cytometry.

RESULTS:
We investigated the naturally occurring Treg-cell response against human LDL in standard chow diet–fed mice that are transgenic for human ApoB100 (apolipoprotein B100). We found that IL (interleukin)-10 expression in LDL-specific T cells from spleen increases with age, albeit LDL-specific populations do not enlarge in older mice. To investigate the generation of IL-10–producing LDL-specific T cells, we transferred naive CD4+ T cells recognizing human ApoB100 from TCR-transgenic mice into human ApoB100-transgenic mice. Adoptive transfer of human ApoB100-specific T cells induced immune tolerance in recipient mice and effectively inhibited activation of subsequently transferred naive T cells of the same specificity in vivo. Moreover, repetitive transfers increased the population of Treg type 1 cells that suppress ApoB100-specific responses via IL-10. In a translational approach, LDL-specific Treg type 1 cells from blood of healthy donors suppressed the activation of monocytic THP-1 cells in an IL-10–dependent manner.

CONCLUSIONS:
We show that repetitive transfer of naive ApoB100-specific T cells and recurrent LDL-specific T-cell stimulation induces Treg type 1 cell–mediated immune tolerance against LDL in vivo. Our results provide insight into the generation of autoantigen-specific anti-inflammatory T cells under tolerogenic conditions.
Periprocedural Mortality in Chronic Total Occlusion Percutaneous Coronary Intervention: Insights From the PROGRESS-CTO Registry
Authors: Simsek Bahadir , Rempakos Athanasios , Kostantinis Spyridon , Karacsonyi Judit , Gorgulu Sevket , Alaswad Khaldoon , Choi James W. , Jaffer Farouc A. , Doshi Darshan , Poommipanit Paul , Aygul Nazif , Krestyaninov Oleg , Khelimskii Dmitrii , Uretsky Barry , Davies Rhian , Goktekin Omer , ElGuindy Ahmed , Jefferson Brian K. , Patel Taral N. , Patel Mitul , Sheikh Abdul , Karmpaliotis Dimitri , Potluri Srinivasa , Al-Azizi Karim , Mastrodemos Olga C. , Rangan Bavana V. , Allana Salman S. , Sandoval Yader , Burke M. Nicholas , Brilakis Emmanouil S. 
Published: June 2023

Background:Death is a rare but devastating complication of chronic total occlusion (CTO) percutaneous coronary intervention.Methods:We examined the clinical characteristics and procedural outcomes of patients who died periprocedurally in the Prospective Global Registry for the Study of CTO Interventions (PROGRESS-CTO).Results:Of the 12 928 patients who underwent CTO percutaneous coronary intervention between 2012 and 2022, 52 (0.4%) died during the index hospitalization. Patients who died were more likely to have a history of heart failure (43% versus 28%;P=0.023). The J-CTO ([Multicenter CTO Registry of Japan]; 2.8±1.1 versus 2.4±1.3;P=0.019), PROGRESS-CTO mortality (2.6±0.9 versus 1.6±1.1;P<0.001), and PROGRESS-CTO pericardiocentesis (2.9±1.1 versus 1.9±1.3;P<0.001) scores were higher in patients who died. In these patients, the use of left ventricular assist devices was also higher (41% versus 3.5%;P<0.001), and retrograde crossing was more often the first crossing strategy (33% versus 13%;P<0.001). The cause of death was cardiac in 43 patients (83%) and noncardiac in 9 patients (17%). Complications leading to cardiac death were: tamponade in 30 patients (58%), acute myocardial infarction in 9 (17.3%), and cardiac arrest/shock in 4 (7.7%). Noncardiac causes of death were: stroke in 3 (5.8%), renal failure in 2 (3.8%), respiratory distress in 2 (3.8%), and hemorrhagic shock in 2 (3.8%).Conclusions:Approximately 0.4% of patients who underwent CTO percutaneous coronary intervention died during the index hospitalization. The main cause of death was tamponade in 58%. PROGRESS-CTO complication scores might help in risk stratification and procedural planning in patients undergoing CTO percutaneous coronary intervention.Registration:URL:https://www.clinicaltrials.gov; Unique Identifier: NCT02061436.
Identifying Contemporary Civil Wars' Effects on Humanitarian
Needs, Responses & Outcomes
Authors: Shesterinina Anastasia 
Published: June 2023

Abstract
Contemporary civil wars are highly complex processes involving a myriad of nonstate, state, civilian, and external actors. These actors develop systems of relationships that evolve during conflict and affect humanitarian needs, responses, and outcomes. This is because humanitarian actors are not isolated from but are part of these social systems. Their activities are constituted by and are constitutive of the interactions between the internal and external actors engaged in civil wars. This essay advances an analytical framework for mapping systems of relationships between the actors at the center of contemporary civil wars to understand how the relationships established by humanitarians transform for reasons outside of their control. This framework highlights the contingency inherent in wartime humanitarian activities in general, and health care provision in particular, and the need for locally informed, adaptive humanitarian practices in changing conflict environments.
Different Electrophysiological Signatures of Similarity-induced and Stroop-like Interference in Language Production
Authors: Pinet Svetlana , Nozari Nazbanou 
Published: June 2023

Abstract
Contextual similarity between targets and competitors, whether semantic or phonological, often leads to behavioral interference in language production. It has been assumed that resolving such interference relies on control processes similar to those involved in tasks such as Stroop. This article tests this assumption by comparing the electrophysiological signatures of interference resulting from a contextual similarity versus a Stroop-like manipulation. In blocks containing two items, participants repeatedly named pictures that were semantically related, phonologically related, or unrelated (contextual similarity manipulation). In straight blocks, the pictures were named by their canonical names. In reverse blocks, participants had to reverse the names (Stroop-like manipulation). Both manipulations led to behavioral interference, but with different electrophysiological profiles. Whole-scalp stimulus-locked and response-locked analyses of semantic and phonological similarity pointed to a system with global modularity with some degree of cascading and interactivity, whereas the effect of phase reversal was sustained and of the opposite polarity. More strikingly, a representational similarity analysis showed a biphasic pattern for Stroop-like reversal, with earlier higher similarity scores for the reverse phase flipping into lower scores ~500 msec poststimulus onset. In contrast, contextual similarity induced higher similarity scores up to articulation. Finally, response-locked mediofrontal components indexing performance monitoring differed between manipulations. Correct response negativity's amplitude was lower in the phonological blocks, whereas a pre-correct response negativity component had higher amplitude in reverse versus straight blocks. These results argue against the involvement of Stroop-like control mechanisms in resolving interference from contextual similarity in language production.
A Dynamic Ordered Logit Model with Fixed Effects
Authors: Muris Chris , Raposo Pedro , Vandoros Sotiris 
Published: June 2023

Abstract
We study a fixed-T panel data logit model for ordered outcomes that accommodates fixed effects and state dependence. We provide identification results for the autoregressive parameter, regression coefficients, and the threshold parameters in this model. Our results require only four observations on the outcome variable. We provide conditions under which a composite conditional maximum likelihood estimator is consistent and asymptotically normal. We use our estimator to explore the determinants of self-reported health in a panel of European countries over the period 2003–2016 and find evidence for state dependence in self-reported health.
The Health Effects of Downsizing Survival
Authors: Ahammer Alexander , Grübl Dominik , Winter-Ebmer Rudolf 
Published: June 2023

Abstract
We show that downsizing has substantial negative effects on the health of workers who remain in the firm. We study mass layoff (ML) survivors in Austria, using workers who survive a ML themselves, but a few years in the future, as a control group. Based on high-quality administrative data, we find evidence that downsizing has persistent effects on mental and physical health, and that these effects can be explained by workers fearing for their own jobs. We also show that health effects due to downsizing imply non-negligible costs for firms.
Can Whistleblowers Root Out Public Expenditure Fraud? Evidence from Medicare
Authors: Leder-Luis Jetson 
Published: June 2023

Abstract
This paper analyzes private anti-fraud enforcement under the False Claims Act, which compensates whistleblowers for litigating against healthcare providers who overbill the US government. I conduct several case studies of successful whistleblower lawsuits concerning Medicare fraud, pairing new legal data with large samples of Medicare claims. I estimate that deterrence from $1.9 billion in whistleblower settlements generated Medicare cost savings of nearly $19 billion, while imposing low costs on the government. These results suggest private enforcement is a cost-effective way to combat public expenditure fraud.
Jarīr and al-Farazdaq’s Naqāʾiḍ Performance
Authors: Jorgensen Cory 
Published: June 2023

Abstract
This article considers the flytings poetry (naqāʾiḍ) of Jarīr and al-Farazdaq (both d. circa 728 CE), which they performed over a period of decades in Basra, Iraq. Described as more entertaining than earlier (pre-Islamic) naqāʾiḍ, why the duo performed this “entertaining” poetry remains a question. I argue that the poets’ goal was to “win” the lampooning contest by amusing their audience. The result is a body of poetry that defended their reputation as performers. Here I analyze passages from Jarīr and al-Farazdaq’s naqāʾiḍ corpus that illustrate how the poets performed an entertaining lampoon for their audience. Central to the discussion is an analogy of their poetry with the modern lampoon genre known as “the Dozens,” which further elucidates the performative aspects of this poetic corpus.
Shifting Centres of Christian Vitality
Authors: Tsekpoe Christian 
Published: June 2023

Abstract
This article highlights for African Pentecostal Christianity some implications of the current shift in the centre of Christian vitality to the south, as well as the rapid growth of Pentecostalism. Through a qualitative analysis of the activities of the Pentecostal-Charismatic movement in Africa, the article explores the implications of the two phenomena for Pentecostal-Charismatic theological education in Africa as well as African Pentecostal-Charismatic leadership. The article concludes by inviting both scholars and practitioners of Pentecostal-Charismatic mission in Africa to take advantage of the opportunities and at the same time confront the challenges facing Pentecostal mission on the continent.
“Ghosts of Missionaries”
Authors: Liutkevičius Eugenijus 
Published: June 2023

Abstract
From the late 1980s, foreign—primarily American—missionaries started to travel to Ukraine in large numbers. This article is concerned with the impact of American Baptist missionaries and how their influence was perceived locally in 2016, the time of my fieldwork. When I set out to conduct my fieldwork research among Baptist believers in Lviv, I was surprised that local believers denied the impact of foreign missionaries on their communities and worship style. Moreover, many local Baptist churchgoers I met claimed they had never encountered an American missionary and insisted that foreign missionaries had not played any significant role in the development and transformation of Ukrainian Baptism. In this article, I present the data from the fieldwork and analyze the Ukrainian Baptists’ reasons for minimizing the influence through the perspective of religioscapes, and glocalization as the dialectic process between homogeneity and heterogeneity.
Commentary—A High Seas Treaty on the Horizon: Progress and Prospects for the Intergovernmental Conference
Authors: Wright Glen , Cremers Klaudija , Rochette Julien 
Published: June 2023

Abstract
After more than a decade of discussions, States at the United Nations are nearing agreement on a new international legally binding instrument for the conservation and sustainable use of biodiversity in marine areas beyond national jurisdiction. The instrument would resolve longstanding questions over the use of marine genetic resources, put in place a process for the des-ignation of marine protected areas, strengthen the framework for environ-mental impact assessment, and enhance capacity building and technology transfer. At the fifth meeting of the Intergovernmental Conference in Au-gust 2022, delegations showed significantly more flexibility and made con-siderable progress towards consensus. Many issues nonetheless remained unresolved and the meeting ultimately could not deliver the clean text needed to negotiate the final trade-offs. This short commentary reviews the progress made, identifies key outstanding issues, and highlights the next steps in the process to finalize the high seas treaty.
Can the World’s Biggest Climate Change Case Help to Save the Ocean?
Authors: Janki Melinda 
Published: June 2023

Abstract
This article examines the first climate change constitutional case in the English-speaking Caribbean. The case challenges the oil and gas buildout offshore Guyana, a new frontier for petroleum. This may be the biggest climate change case to date based on the amount of greenhouse gas pollu-tion at stake or on the amount of potential liability arising from harm to the ocean. The article locates the case in current climate litigation. However, it characterizes the problem as greenhouse gas pollution and not climate change, which it treats as a symptom. The case raises interesting questions about the court’s obligation to take into account international law in deter-mining the scope of the State’s constitutional duty to citizens for a healthy environment. It also flags the difficulty of applying international law to determine the climate obligations of a carbon sink. The case is ongoing.