bluuebunny/crossref_metadata_2025 huggingface dataset:
Measuring the Relationship Between the 2019 Title X Final Rule and Patients’ Sexual and Reproductive Health Care Access and Behavior in Iowa Using a Difference-in-Difference Approach
Authors: Kavanaugh Megan L. , Leong Ellie , Haas Madeleine
Published: October 2023

Introduction

Previous research has documented how the implementation of the 2019 Title X Final Rule reduced the Title X network capacity and led to decreases in patient numbers. Our objective was to examine the relationship between the Rule and patients’ reproductive health care access and outcomes.

Methods

Our analysis draws on panel data from patients recruited when seeking publicly funded family planning care in Iowa between May 2018 and February 2019 who completed a baseline survey and agreed to be contacted for follow-up surveys at 6-, 12-, 18-, and/or 24-month intervals. We employ a difference-in-difference (DiD) approach, comparing reproductive health outcomes (access to care and contraceptive use) of respondents who had recently received care at sites that eventually left the Title X system following the Rule, the exposed group, to outcomes among those who had recently received care at sites that did not shift from being in the Title X system to exiting it, the control group, both before and after its implementation.

Results

After adjusting for respondents’ demographic characteristics in the DiD models, we found that those in the exposure group were 11% less likely to have received recent contraceptive care compared to respondents in the control group after the implementation of the Title X Final Rule when examining the full study period (p < .01). When examining only the pre-COVID 19 time period, we found that respondents in the exposure group were 13% less likely to have been using a provider-involved method (p < 0.01), 11% less likely to have been using a method that carries a cost (p < 0.05), and 18% less likely to report being satisfied with their method (p < 0.001) compared to respondents in the control group.

Conclusions

Using Iowa as a case study to understand how the 2019 Title X Final Rule may have changed family planning patients’ sexual and reproductive health outcomes, we found evidence of a negative association of the Rule with patients’ access to, and use of, contraception.

Policy Implications

These findings expand the evidence base of the influence of the 2019 Title X Final Rule on the Title X health care system and its capacity to provide SRH care by highlighting the trickle-down effects of the Rule on patients themselves. Policies that restrict access to any aspect of sexual and reproductive health care, including contraception and abortion, are in direct conflict with people’s realization of reproductive autonomy.
Maximal Number of Repetitions at Percentages of the One Repetition Maximum: A Meta-Regression and Moderator Analysis of Sex, Age, Training Status, and Exercise
Authors: Nuzzo James L. , Pinto Matheus D. , Nosaka Kazunori , Steele James
Published: October 2023

The maximal number of repetitions that can be completed at various percentages of the one repetition maximum (1RM) [REPS ~ %1RM relationship] is foundational knowledge in resistance exercise programming. The current REPS ~ %1RM relationship is based on few studies and has not incorporated uncertainty into estimations or accounted for between-individuals variation. Therefore, we conducted a meta-regression to estimate the mean and between-individuals standard deviation of the number of repetitions that can be completed at various percentages of 1RM. We also explored if the REPS ~ %1RM relationship is moderated by sex, age, training status, and/or exercise. A total of 952 repetitions-to-failure tests, completed by 7289 individuals in 452 groups from 269 studies, were identified. Study groups were predominantly male (66%), healthy (97%), < 59 years of age (92%), and resistance trained (60%). The bench press (42%) and leg press (14%) were the most commonly studied exercises. The REPS ~ %1RM relationship for mean repetitions and standard deviation of repetitions were best described using natural cubic splines and a linear model, respectively, with mean and standard deviation for repetitions decreasing with increasing %1RM. More repetitions were evident in the leg press than bench press across the loading spectrum, thus separate REPS ~ %1RM tables were developed for these two exercises. Analysis of moderators suggested little influences of sex, age, or training status on the REPS ~ %1RM relationship, thus the general main model REPS ~ %1RM table can be applied to all individuals and to all exercises other than the bench press and leg press. More data are needed to develop REPS ~ %1RM tables for other exercises.
Islandness and the European Court of Human Rights: Marooning Rights on Islands?
Authors: Tsampi Aikaterini
Published: October 2023

Some 80 million people live on European islands. It thus comes as no surprise that a number of cases brought before the European Court of Human Rights developed on and/or pertain to islands. What is surprising, though, is that this jurisprudential corpus has not been explored with a view to assessing whether islandness has or should have a role in the implementation of the European Convention on Human Rights on islands. The present paper contemplates the strengths of an islandness-based approach in the implementation of human rights through the mapping of the weaknesses, the potentials and the lost opportunities in the case law of the Court with respect to such an approach. In this context, findings from the field of Island Studies are also considered. By focusing on the ECHR habitat, the present paper exemplifies, in particular, the untapped potential of an islandness-based approach in the development of international human rights law in general.
Emotions Online: Exploring Knowledge Workers’ Emotional Labour in a Digital Context in an Agile IT Company
Authors: Pultz Sabina , Dupret Katia
Published: October 2023

Digital technologies and new ways of organising transform the way we experience work. This paper seeks to contribute to our understanding of the role of digital emotional labour (EL) among knowledge workers. We investigate the EL involved in digital communication practices among co-located knowledge workers employed in an agile IT-consultancy firm with a relatively flat hierarchy. Based on rich qualitative data, we analyse how the specific socio-material infrastructures of a democratic communication technology called ‘Flowdock’ give rise to EL (Hochschild inAmerican Journal of Sociology, 85(3), 551–575, 1979, University of California Press, 1983). The study contributes theoretically by developing work on EL in a digital context by engaging with Oudshoorn’s (Sociology of Health & Illness, 31(3), 390–405, 2009) term ‘digital proximity’. This implies opening up EL to a more dynamic and situated approach and contributing to the organisational research scrutinising the EL of backstage professionals. The paper concludes that online communication creates new demands of managing emotions in relation to 4 themes key to agile organising: (1) working as whole persons, (2) creating partnerships, (3) unclear decision-making and lastly (4) informal power dynamics. We discuss implications of the overall finding that knowledge workers face increased demands mixing social and technical skills.
A Metastasis of Ovarian Cancer in the Bartholin Gland: A Case Report with Systematic Literature Review
Authors: Olmes Gregor Leonhard , Breitbach Georg Peter , Tepikin Anton , Nistor Adriana , Solomayer Erich Franz , Hamoud Bashar Haj
Published: October 2023

The metastasis of a gynecological malignancy to the Bartholin gland is rare. We report the case of a 62-year-old patient who had undergone extensive treatment of metastatic ovarian cancer that involved the liver, spleen, and peritoneum. She presented with painful swelling of the left vulva. Clinical and sonographic examinations showed a solid tumor in loco typico of the Bartholin gland. Surgical excision was performed. The patient died 3 months after the diagnosis of this metastasis. We performed a systematic search of PubMed, which yielded 453 entries. We selected those with at least an abstract available in English that described metastatic lesions on the Bartholin gland (n = 5). The review showed that a variety of primary cancers (colorectal, medullary thyroid, breast cancer, and endometrial cancers) metastasize to this location. Some patients showed signs of visceral metastasis. Bartholin gland metastases appeared as initial and metachronous manifestations. Most patients were symptomatic, with painful swelling or abscess. Genetic alterations were mentioned in some cases. The main pathways of metastasis discussed were lymphatic, but the mechanism of such metastasis remains unclear. Surgical resection was the preferred treatment option. The literature review indicated that Bartholin gland metastasis of ovarian cancer is rare and associated with poor prognosis. Oncological reasons for vulvar pathologies should be taken into consideration in patients with metastases.
Transformer and Graph Convolutional Network for Text Classification
Authors: Liu Boting , Guan Weili , Yang Changjin , Fang Zhijie , Lu Zhiheng
Published: October 2023

Graph convolutional network (GCN) is an effective tool for feature clustering. However, in the text classification task, the traditional TextGCN (GCN for Text Classification) ignores the context word order of the text. In addition, TextGCN constructs the text graph only according to the context relationship, so it is difficult for the word nodes to learn an effective semantic representation. Based on this, this paper proposes a text classification method that combines Transformer and GCN. To improve the semantic accuracy of word node features, we add a part of speech (POS) to the word-document graph and build edges between words based on POS. In the layer-to-layer of GCN, the Transformer is used to extract the contextual and sequential information of the text. We conducted the experiment on five representative datasets. The results show that our method can effectively improve the accuracy of text classification and is better than the comparison method.
Advances in airway management in recent 10 years from 2013 to 2023
Authors: Liu Yurui , He Yuewen , Wang Xia , Li Jingjing , Zhang Zhengze , Zhuang Xuhui , Liu Hao , Li Ruogen , Liu Huihui , Zhuang Yuerong , Wang Qiong , Tang Zhihang , Wang Yong , Ma Wuhua
Published: October 2023

Difficult airway management has been the focus in the field of anesthesiology. Clinical research in difficult airway management has made some progress in the last 10 years. We searched the relevant literature and summarized the latest clinical research in the field of difficult airway management in this review to provide some practice strategies for difficult airway management for anesthesiologists as well as a range of professionals.

Graphical Abstract
The Collaborative Congress
Authors: Craig Alison W.
Published: October 2023

The Collaborative Congress is an in-depth study of how members work together to create policy in a polarized legislature. While the modern Congress is characterized by partisanship and conflict, members frequently look for opportunities to find common ground on substantive policy. This book challenges the conventional narrative of a hopelessly dysfunctional legislature by revealing the widespread use of collaboration for successful policymaking. Drawing on a new dataset of communication between members, social network analysis, and qualitative interviews, chapters demonstrate that nearly every member engages in collaboration across a broad array of issues. The book identifies the strategic and political considerations that influence a member's decision to collaborate and shows that collaborative legislation is more successful at every stage of the policymaking process. This title is part of the Flip it Open Programme and may also be available Open Access. Check our website Cambridge Core for details.
Precarious work and challenger parties: how precarity influenced vote choice in the 2018 Italian election
Authors: Girardi Elisabetta
Published: October 2023

Across Western European democracies, the last 20 years have seen a growth of precarious employment and the rise of challenger parties. Both trends are especially marked in Italy, where occupational insecurity has become the norm and over half of the electorate has turned to a challenger party. In this article, I investigate the relationship between these two phenomena, addressing the question of whether and how precarity in the labor market influenced vote choice in the 2018 general election. First, I provide descriptive evidence that the Italian labor market shifted from dualism to generalized precarization. Second, I empirically investigate the relationship between precarity and voting in this context. The results show that the perception of precarity, not formal employment status, influenced voting behavior: it fostered participation, increased support for the Five Star Movement, and decreased support for the Democratic Party. These findings challenge core assumptions in the literature, first and foremost about precarious workers' low turnout rate, difficult mobilization, and consequent political irrelevance. They indicate that the electoral weight of precarious workers has increased, and their representation can be electorally beneficial.
Apparent singularities of the finite-depth Zakharov equation
Authors: Pezzutto Paolo , Shrira Victor I.
Published: October 2023

The description of weakly nonlinear water-wave evolution over a horizontal bottom by the integro-differential Zakharov equation, because of utilising the underlying Hamiltonian structure, has many advantages over direct use of the Euler equations. However, its application to finite-depth situations is not straightforward since, in contrast to the deep-water case, the kernels governing the four-wave interactions are singular, as well as the kernels in the canonical transformation that removes non-resonant interactions from the original equations of motion. At the singularities, these kernels are finite but not unique. The issue of how to use the Zakharov equation for finite depth and whether it is possible at all was debated intensely in the literature for decades but remains outstanding. Here we show that the absence of a limit of the kernels at the singularities is inconsequential, since in the equations of motion it is only the integral that matters. By applying the definition of the Dirac-

$\delta$

, we show that all the integrals involving a trivial manifold singularity are evaluated uniquely. Therefore, the Zakharov evolution equation and the nonlinear canonical transformation are only apparently singular. The findings are validated by application to examples where predictions based on the Zakharov equation are compared with known solutions obtained from the Euler equations.
Pandemic science and commercial values: An institutional account of values in science
Authors: Fernández Pinto Manuela
Published: October 2023

The different social institutions involved in the development and distribution of science and technology tend to promote, primarily, commercial and private interests, even in situations with high social stakes. Acknowledging how these interests interplay with social and epistemic values is fundamental for understanding the role of values in science today. To show this, I use the global pandemic and the race to develop and distribute vaccines against COVID-19 as an example. I argue that a mere circumstantial alignment of values across the social institutions of science is not enough and that instead we need a more substantive alignment.
Where memory resides: Is there a rivalry between molecular and synaptic models of memory?
Authors: Colaço David , Najenson Jonathan
Published: October 2023

Recent proposals that the substrate of memory is molecular raise questions about where this molecular model stands in relation to the dominant synaptic model of memory. In this article, we address the perceived rivalry between these models and ask whether they can be integrated. We argue that addressing rivalry or integration requires delineating the explananda of synaptic and molecular models, as well as revisiting assumptions about how these models account for their explananda. The perceived rivalry between these models exemplifies epistemic costs that arise when we try to pit explanatory models as rivals or integrate them.
Structuring Institutions for Responsible and Accountable Science
Authors: Douglas Heather
Published: October 2023

Oversight institutions that hold science and scientists accountable for responsible science have thus far not focused on the general societal impact of science. Responsibility for societal impact is now a pervasive aspect of scientific practice, but accountability remains elusive. I argue here that we should proceed cautiously, and that only clear and precise floors for responsibility should have accountability mechanisms. For the remainder of societal responsibilities in science, we should institutionalize assistive ethical mechanisms, which help scientists meet their responsibilities and share rather than offload ethical labor.
Moral emotions underlie puritanical morality
Authors: Zhu Ruida , Liu Chao
Published: October 2023

Fitouchi et al. illustrate the cognitive and evolutionary foundations of puritanical morality, while leave the emotional foundation unclear. We complement their theory by proposing moral emotions (e.g., guilt and shame) as characteristic emotions underlying puritanical morality. Our proposition is based on the findings that these moral emotions emerge after violations of puritanical norms and promote self-control and cooperation.
Purity is not a distinct moral domain
Authors: Kollareth Dolichan , Russell James A.
Published: October 2023

Purity violations overlap with other moral domains. They are not uniquely characterized by hypothesized markers of purity – the witness's emotion of disgust, taint to perpetrator's soul, or the diminished role of intention in moral judgment. Thus, Fitouchi et al.'s proposition that puritanical morality (a subset of violations in the purity domain) is part of cooperation-based morality is an important advance.
A broader theory of cooperation can better explain “purity”
Authors: Curry Oliver Scott , Sznycer Daniel
Published: October 2023

Self-control provides one cooperative explanation for “purity.” Other types of cooperation provide additional explanations. For example, individuals compete for status by displaying high-value social and sexual traits, which are moralised because they reduce the mutual costs of conflict. As this theory predicts, sexually unattractive traits are perceived as morally bad, aside from self-control. Moral psychology will advance more quickly by drawing on all theories of cooperation.
Drinking and feasting are perceived as facilitating cooperation
Authors: Fu Yuhan , Viera Gerardo
Published: October 2023

We argue that the occurrence of puritanical norms cannot simply be explained by appealing to the need for cooperation. Anthropological and archaeological studies suggest that across history and cultures’ self-indulgent behaviours, such as excessive drinking, eating, and feasting, have been used to enhance cooperation by enforcing social and group identities.
The Development of Abstract Word Meanings
Authors: MURAKI Emiko J. , REGGIN Lorraine D. , FEDDEMA Carissa Y. , PEXMAN Penny M.
Published: October 2023

Extensive research has shown that children’s early words are learned through sensorimotor experience. Thus, early-acquired words tend to have more concrete meanings. Abstract word meanings tend to be learned later but less is known about their acquisition. We collected meaning-specific concreteness ratings and examined their relationship with age-of-acquisition data from large-scale vocabulary testing with children in grade 2 to college age. Earlier-acquired meanings were rated as more concrete while later-acquired meanings as more abstract, particularly for words typically considered to be concrete. The results suggest that sensorimotor experiences are important to early-acquired word meanings, and other experiences (e.g., linguistic) are important to later-acquired meanings, consistent with a multi-representational view of lexical semantics.
The effect of albumın and total proteın values as nutrıtıonal markers after Fontan surgery on prognosıs
Authors: Kara Kenan Abdurrahman , Arslanoğlu Ergin , Yigit Fatih , Arkan Cuneyt , Yılmaz Abdullah Arif , Akardere Ömer Faruk , Cine Nihat , Tuncer Eylem , Çetiner Nilüfer , Ceyran Hakan
Published: October 2023

Introduction:

Children with CHD develop heart failure due to increased pulmonary blood flow, cyanosis, and pulmonary hypertension. The metabolic needs of these children differ from those of healthy children, and malnutrition is common. Protein-losing enteropathy has been reported in 5 to 13% of patients after the Fontan procedure. Serum albumin and total protein levels, which are indicators of the quality of post-operative care, can be useful tools for monitoring and examining the intensive care treatment strategies of these patients. In our retrospective study, the effects of albumin and total protein values, which are two of the markers that give us an idea about diet, nutritional status, and inflammation, on the prognosis of children who underwent the Fontan procedure were investigated.

Method:

In our study, 127 patients who underwent Fontan procedure in our clinic between 2012 and 2021 were analysed retrospectively. Of the patients, 52.7% (n = 67) were male and 47.3% (n = 60) were female. The mean age is 5.83 ± 4.63 years. Patients who underwent albumin replacement were not included in the study.

Results:

Although the relationship between pre-operative albumin and total protein values and post-operative mortality was not statistically significant, the inverse correlation of post-operative albumin 1st, 2nd, and 3rd-day values and post-operative total protein 1st, 2nd, and 3rd-day values with mortality was found to be statistically significant. In addition, we found that mortality was statistically high in patients whose total protein amount was below 6.65 mg/dl in the early post-operative period.

Conclusion:

Albumin and total protein, whose blood levels can vary with diet, can be used as predictors in the early post-operative prognosis of Fontan patients. In addition, when we examined the exitus patients, it was observed that the total protein amount was below 6.65 mg/dl on the post-operative 1st day. Based on this, we think that a diet with high protein content before surgery will help reduce post-operative early mortality.
If Not Now, Then When? Pathways to Embed Climate Change Within Social Policy
Authors: Snell Carolyn , Anderson Sara , Thomson Harriet
Published: October 2023

Climate change is arguably the defining issue of our time, with global impacts. Yet to date, scholarship within social policy has remained relatively fragmented and disparate, leaving an urgent need to start comprehensively embedding environmental thinking across all domains of the discipline (Williams, 2021). Responding to this challenge, this paper draws together existing work at the nexus of social policy, the environment, and climate change. The paper then presents findings from workshops held with social policy scholars, policymakers, and practitioners, using these discussions to propose pathways to embed climate change within the discipline. The paper represents a significant contribution to knowledge within the field as it seeks to both broaden discussions about social policy and climate change; to identify theoretical and empirical relationships that exist between the two fields but have not been fully recognised in existing scholarship; and to bring new perspectives and voices into the discussion.
Making a Case for Centring Energy Poverty in Social Policy in Light of the Climate Emergency: A Global Integrative Review
Authors: Stojilovska Ana , Thomson Harriet , Mejía-Montero Adolfo
Published: October 2023

The recent polycrises of COVID-19, economic recession, and energy price increases have reinforced the critical importance of energy services – such as heating, information and communications technology, and refrigeration – to everyday societal functioning. Compromising access to these energy services, or energy poverty, limits social and economic development affecting education, health, and social participation. Energy poverty is impacted by climate change and climate-related policies – however, this nexus has been marginalised within social policy. We critically review literature at the intersection of climate change and energy poverty identifying policy approaches, tensions, and solutions of relevance for social policy. While tensions exist between efforts to mitigate climate change and energy poverty, climate-friendly mitigation of energy poverty requires better integration of social perspectives to disrupt current technical biases, recognising the characteristics and needs of individuals in energy poverty, and holistic governance approaches, especially involving the health and housing sectors.
Modeling study of the effect of placebo and medical therapy on storage and voiding symptoms, nocturia, and quality of life in men with prostate enlargement at risk for progression
Authors: Gravas Stavros , Manuel-Palacios Juan , Chavan Chandrashekhar , Roehrborn Claus G. , Oelke Matthias , Averbeck Marcio Augusto , Biswas Arunangshu , García Llenalia María , Mohamed Khadeeja , Cortes Vanessa
Published: October 2023

Background

Modeling studies using large datasets from men with lower urinary tract symptoms/benign prostate enlargement (LUTS/BPE) can predict changes in International Prostate Symptom Score (IPSS) and risk of acute urinary retention/surgery under different treatment regimens and according to predictors (baseline characteristics) that commonly define risk of progression. We assessed the impact of treatments on different symptom types (storage, voiding, and nocturia), quality of life (QoL; IPSS Q8), and BPH Impact Index [BII]).

Methods

Generalized least squares models were used to predict each outcome. Data from the CombAT study were used to predict outcomes for active treatments (dutasteride, tamsulosin, combination therapy). Predictors included: age; IPSS total, storage, voiding, nocturia and QoL (IPSS Q8) scores; BII; prostate volume; maximum urine flow rate (Qmax), prostate-specific antigen, postvoid residual urine (PVR); alpha-blocker usage within 12 months. Data from phase III dutasteride monotherapy studies were used to predict placebo outcomes. Results were visualized using an interactive web-based tool (www.bphtool.com).

Results

Combination therapy provided greater predicted benefit than either monotherapy for all five outcomes for most patient profiles within the CombAT inclusion criteria. PVR and corresponding subscores were significant predictors of change in both storage and voiding subscores. Alpha-blocker use within 12 months, age (storage subscore), and Qmax (voiding subscore) were also significant predictors. PVR, age, Qmax, and nocturia score were significant predictors of change in nocturia. PVR, Qmax, previous alpha-blocker use, total IPSS, and QoL (IPSS Q8) score were significant predictors of change in QoL (IPSS Q8) score. For BII, significant predictors were PVR, age, total IPSS, and BII score. The multivariable effect of covariates and treatments is best visualized through the interactive web-based tool.

Conclusions

This predictive modeling study informs our understanding of how risk factors for disease progression interact and affect treatment impact on different symptom types and QoL scores.
Protistan predation selects for antibiotic resistance in soil bacterial communities
Authors: Nguyen Thi Bao-Anh , Bonkowski Michael , Dumack Kenneth , Chen Qing-Lin , He Ji-Zheng , Hu Hang-Wei
Published: October 2023

Understanding how antibiotic resistance emerges and evolves in natural habitats is critical for predicting and mitigating antibiotic resistance in the context of global change. Bacteria have evolved antibiotic production as a strategy to fight competitors, predators and other stressors, but how predation pressure of their most important consumers (i.e., protists) affects soil antibiotic resistance genes (ARGs) profiles is still poorly understood. To address this gap, we investigated responses of soil resistome to varying levels of protistan predation by inoculating low, medium and high concentrations of indigenous soil protist suspensions in soil microcosms. We found that an increase in protistan predation pressure was strongly associated with higher abundance and diversity of soil ARGs. High protist concentrations significantly enhanced the abundances of ARGs encoding multidrug (oprJ and ttgB genes) and tetracycline (tetV) efflux pump by 608%, 724% and 3052%, respectively. Additionally, we observed an increase in the abundance of numerous bacterial genera under high protistan pressure. Our findings provide empirical evidence that protistan predation significantly promotes antibiotic resistance in soil bacterial communities and advances our understanding of the biological driving forces behind the evolution and development of environmental antibiotic resistance.
A taxonomy of early diagnosis research to guide study design and funding prioritisation
Authors: Whitfield Emma , White Becky , Denaxas Spiros , Barclay Matthew E. , Renzi Cristina , Lyratzopoulos Georgios
Published: October 2023

Researchers and research funders aiming to improve diagnosis seek to identify if, when, where, and how earlier diagnosis is possible. This has led to the propagation of research studies using a wide range of methodologies and data sources to explore diagnostic processes. Many such studies use electronic health record data and focus on cancer diagnosis. Based on this literature, we propose a taxonomy to guide the design and support the synthesis of early diagnosis research, focusing on five key questions:

Do healthcare use patterns suggest earlier diagnosis could be possible?

How does the diagnostic process begin?

How do patients progress from presentation to diagnosis?

How long does the diagnostic process take?

Could anything have been done differently to reach the correct diagnosis sooner?

We define families of diagnostic research study designs addressing each of these questions and appraise their unique or complementary contributions and limitations. We identify three further questions on relationships between the families and their relevance for examining patient group inequalities, supported with examples from the cancer literature. Although exemplified through cancer as a disease model, we recognise the framework is also applicable to non-neoplastic disease. The proposed framework can guide future study design and research funding prioritisation.
Autophagy: Regulator of cell death
Authors: Liu ShiZuo , Yao ShuaiJie , Yang Huan , Liu ShuaiJie , Wang YanJiao
Published: October 2023

Autophagy is the process by which cells degrade and recycle proteins and organelles to maintain intracellular homeostasis. Generally, autophagy plays a protective role in cells, but disruption of autophagy mechanisms or excessive autophagic flux usually leads to cell death. Despite recent progress in the study of the regulation and underlying molecular mechanisms of autophagy, numerous questions remain to be answered. How does autophagy regulate cell death? What are the fine-tuned regulatory mechanisms underlying autophagy-dependent cell death (ADCD) and autophagy-mediated cell death (AMCD)? In this article, we highlight the different roles of autophagy in cell death and discuss six of the main autophagy-related cell death modalities, with a focus on the metabolic changes caused by excessive endoplasmic reticulum-phagy (ER-phagy)-induced cell death and the role of mitophagy in autophagy-mediated ferroptosis. Finally, we discuss autophagy enhancement in the treatment of diseases and offer a new perspective based on the use of autophagy for different functional conversions (including the conversion of autophagy and that of different autophagy-mediated cell death modalities) for the clinical treatment of tumors.
PACS-2 deficiency aggravates tubular injury in diabetic kidney disease by inhibiting ER-phagy
Authors: Yang Jinfei , Li Li , Li Chenrui , Chen Wei , Liu Yan , Luo Shilu , Zhao Chanyue , Han Yachun , Yang Ming , Zhao Hao , Jiang Na , Xi Yiyun , Tang Chengyuan , Cai Juan , Xiao Li , Liu Huafeng , Sun Lin
Published: October 2023

Autophagy of endoplasmic reticulum (ER-phagy) selectively removes damaged ER through autophagy-lysosome pathway, acting as an adaptive mechanism to alleviate ER stress and restore ER homeostasis. However, the role and precise mechanism of ER-phagy in tubular injury of diabetic kidney disease (DKD) remain obscure. In the present study, we demonstrated that ER-phagy of renal tubular cells was severely impaired in streptozocin (STZ)-induced diabetic mice, with a decreased expression of phosphofurin acidic cluster sorting protein 2 (PACS-2), a membrane trafficking protein which was involved in autophagy, and a reduction of family with sequence similarity 134 member B (FAM134B), one ER-phagy receptor. These changes were further aggravated in mice with proximal tubule specific knockout of Pacs-2 gene. In vitro, transfection of HK-2 cells with PACS-2 overexpression plasmid partially improved the impairment of ER-phagy and the reduction of FAM134B, both of which were induced in high glucose ambience; while the effect was blocked by FAM134B siRNA. Mechanistically, PACS-2 interacted with and promoted the nuclear translocation of transcription factor EB (TFEB), which was reported to activate the expression of FAM134B. Collectively, these data unveiled that PACS-2 deficiency aggravates renal tubular injury in DKD via inhibiting ER-phagy through TFEB/FAM134B pathway.
Large-scale plasma proteomics comparisons through genetics and disease associations
Authors: Eldjarn Grimur Hjorleifsson , Ferkingstad Egil , Lund Sigrun H. , Helgason Hannes , Magnusson Olafur Th. , Gunnarsdottir Kristbjorg , Olafsdottir Thorunn A. , Halldorsson Bjarni V. , Olason Pall I. , Zink Florian , Gudjonsson Sigurjon A. , Sveinbjornsson Gardar , Magnusson Magnus I. , Helgason Agnar , Oddsson Asmundur , Halldorsson Gisli H. , Magnusson Magnus K. , Saevarsdottir Saedis , Eiriksdottir Thjodbjorg , Masson Gisli , Stefansson Hreinn , Jonsdottir Ingileif , Holm Hilma , Rafnar Thorunn , Melsted Pall , Saemundsdottir Jona , Norddahl Gudmundur L. , Thorleifsson Gudmar , Ulfarsson Magnus O. , Gudbjartsson Daniel F. , Thorsteinsdottir Unnur , Sulem Patrick , Stefansson Kari
Published: October 2023

High-throughput proteomics platforms measuring thousands of proteins in plasma combined with genomic and phenotypic information have the power to bridge the gap between the genome and diseases. Here we performed association studies of Olink Explore 3072 data generated by the UK Biobank Pharma Proteomics Project1 on plasma samples from more than 50,000 UK Biobank participants with phenotypic and genotypic data, stratifying on British or Irish, African and South Asian ancestries. We compared the results with those of a SomaScan v4 study on plasma from 36,000 Icelandic people2, for 1,514 of whom Olink data were also available. We found modest correlation between the two platforms. Although cis protein quantitative trait loci were detected for a similar absolute number of assays on the two platforms (2,101 on Olink versus 2,120 on SomaScan), the proportion of assays with such supporting evidence for assay performance was higher on the Olink platform (72% versus 43%). A considerable number of proteins had genomic associations that differed between the platforms. We provide examples where differences between platforms may influence conclusions drawn from the integration of protein levels with the study of diseases. We demonstrate how leveraging the diverse ancestries of participants in the UK Biobank helps to detect novel associations and refine genomic location. Our results show the value of the information provided by the two most commonly used high-throughput proteomics platforms and demonstrate the differences between them that at times provides useful complementarity.
The PTPN2/PTPN1 inhibitor ABBV-CLS-484 unleashes potent anti-tumour immunity
Authors: Baumgartner Christina K. , Ebrahimi-Nik Hakimeh , Iracheta-Vellve Arvin , Hamel Keith M. , Olander Kira E. , Davis Thomas G. R. , McGuire Kathleen A. , Halvorsen Geoff T. , Avila Omar I. , Patel Chirag H. , Kim Sarah Y. , Kammula Ashwin V. , Muscato Audrey J. , Halliwill Kyle , Geda Prasanthi , Klinge Kelly L. , Xiong Zhaoming , Duggan Ryan , Mu Liang , Yeary Mitchell D. , Patti James C. , Balon Tyler M. , Mathew Rebecca , Backus Carey , Kennedy Domenick E. , Chen Angeline , Longenecker Kenton , Klahn Joseph T. , Hrusch Cara L. , Krishnan Navasona , Hutchins Charles W. , Dunning Jax P. , Bulic Marinka , Tiwari Payal , Colvin Kayla J. , Chuong Cun Lan , Kohnle Ian C. , Rees Matthew G. , Boghossian Andrew , Ronan Melissa , Roth Jennifer A. , Wu Meng-Ju , Suermondt Juliette S. M. T. , Knudsen Nelson H. , Cheruiyot Collins K. , Sen Debattama R. , Griffin Gabriel K. , Golub Todd R. , El-Bardeesy Nabeel , Decker Joshua H. , Yang Yi , Guffroy Magali , Fossey Stacey , Trusk Patricia , Sun Im-Meng , Liu Yue , Qiu Wei , Sun Qi , Paddock Marcia N. , Farney Elliot P. , Matulenko Mark A. , Beauregard Clay , Frost Jennifer M. , Yates Kathleen B. , Kym Philip R. , Manguso Robert T.
Published: October 2023

Immune checkpoint blockade is effective for some patients with cancer, but most are refractory to current immunotherapies and new approaches are needed to overcome resistance1,2. The protein tyrosine phosphatases PTPN2 and PTPN1 are central regulators of inflammation, and their genetic deletion in either tumour cells or immune cells promotes anti-tumour immunity3–6. However, phosphatases are challenging drug targets; in particular, the active site has been considered undruggable. Here we present the discovery and characterization of ABBV-CLS-484 (AC484), a first-in-class, orally bioavailable, potent PTPN2 and PTPN1 active-site inhibitor. AC484 treatment in vitro amplifies the response to interferon and promotes the activation and function of several immune cell subsets. In mouse models of cancer resistant to PD-1 blockade, AC484 monotherapy generates potent anti-tumour immunity. We show that AC484 inflames the tumour microenvironment and promotes natural killer cell and CD8+ T cell function by enhancing JAK–STAT signalling and reducing T cell dysfunction. Inhibitors of PTPN2 and PTPN1 offer a promising new strategy for cancer immunotherapy and are currently being evaluated in patients with advanced solid tumours (ClinicalTrials.gov identifier NCT04777994). More broadly, our study shows that small-molecule inhibitors of key intracellular immune regulators can achieve efficacy comparable to or exceeding that of antibody-based immune checkpoint blockade in preclinical models. Finally, to our knowledge, AC484 represents the first active-site phosphatase inhibitor to enter clinical evaluation for cancer immunotherapy and may pave the way for additional therapeutics that target this important class of enzymes.
Rock organic carbon oxidation CO2 release offsets silicate weathering sink
Authors: Zondervan Jesse R. , Hilton Robert G. , Dellinger Mathieu , Clubb Fiona J. , Roylands Tobias , Ogrič Mateja
Published: October 2023

Mountain uplift and erosion have regulated the balance of carbon between Earth’s interior and atmosphere, where prior focus has been placed on the role of silicate mineral weathering in CO2 drawdown and its contribution to the stability of Earth’s climate in a habitable state1–5. However, weathering can also release CO2 as rock organic carbon (OCpetro) is oxidized at the near surface6,7; this important geological CO2 flux has remained poorly constrained3,8. We use the trace element rhenium in combination with a spatial extrapolation model to quantify this flux across global river catchments3,9. We find a CO2 release of $${68}_{-6}^{+18}$$

68

−
6

+
18

megatons of carbon annually from weathering of OCpetro in near-surface rocks, rivalling or even exceeding the CO2 drawdown by silicate weathering at the global scale10. Hotspots of CO2 release are found in mountain ranges with high uplift rates exposing fine-grained sedimentary rock, such as the eastern Himalayas, the Rocky Mountains and the Andes. Our results demonstrate that OCpetro is far from inert and causes weathering in regions to be net sources or sinks of CO2. This raises questions, not yet fully studied, as to how erosion and weathering drive the long-term carbon cycle and contribute to the fine balance of carbon fluxes between the atmosphere, biosphere and lithosphere2,11.
Sialoglycan binding triggers spike opening in a human coronavirus
Authors: Pronker Matti F. , Creutznacher Robert , Drulyte Ieva , Hulswit Ruben J. G. , Li Zeshi , van Kuppeveld Frank J. M. , Snijder Joost , Lang Yifei , Bosch Berend-Jan , Boons Geert-Jan , Frank Martin , de Groot Raoul J. , Hurdiss Daniel L.
Published: October 2023

Coronavirus spike proteins mediate receptor binding and membrane fusion, making them prime targets for neutralizing antibodies. In the cases of severe acute respiratory syndrome coronavirus, severe acute respiratory syndrome coronavirus 2 and Middle East respiratory syndrome coronavirus, spike proteins transition freely between open and closed conformations to balance host cell attachment and immune evasion1–5. Spike opening exposes domain S1B, allowing it to bind to proteinaceous receptors6,7, and is also thought to enable protein refolding during membrane fusion4,5. However, with a single exception, the pre-fusion spike proteins of all other coronaviruses studied so far have been observed exclusively in the closed state. This raises the possibility of regulation, with spike proteins more commonly transitioning to open states in response to specific cues, rather than spontaneously. Here, using cryogenic electron microscopy and molecular dynamics simulations, we show that the spike protein of the common cold human coronavirus HKU1 undergoes local and long-range conformational changes after binding a sialoglycan-based primary receptor to domain S1A. This binding triggers the transition of S1B domains to the open state through allosteric interdomain crosstalk. Our findings provide detailed insight into coronavirus attachment, with possibilities of dual receptor usage and priming of entry as a means of immune escape.
Probing corrosion using a simple and versatile in situ multimodal corrosion measurement system
Authors: Niverty Sridhar , Kalsar Rajib , Seffens Robert J. , Guzman Anthony D. , Roosendaal Timothy J. , Strange Lyndi , Joshi Vineet V.
Published: October 2023

In this work, we have developed a unique in situ multimodal corrosion system that is capable of acquiring electrochemical data, sample imaging/visualization and hydrogen collection, simultaneously. Each of these modalities yield valuable information pertaining to the ongoing corrosion process. Combining them can yield holistic information on the role of microstructure, processing history, presence of coatings, etc., on the sequence of steps occurring during the corrosion process, and how they correlate with the acquired electrochemical data. Four materials systems, namely AA6061-T6 aluminum alloy, AZ91 magnesium alloy, galvanized DP590 steel, and pure Zn, were investigated under open circuit potential and under potentiodynamic polarization. The multimodal corrosion system was utilized to observe processes such as surface passivation and dissolution, pit and filiform corrosion initiation and propagation, and was correlated with location and magnitude of hydrogen evolution. This approach is shown to yield a truly multimodal understanding of the ongoing corrosion processes.
Vision protection therapy for prevention of neovascular age-related macular degeneration
Authors: Luttrull Jeffrey K. , Gray Gerry , Bhavan Sathy V.
Published: October 2023

To access the effect of vision protection therapy on neovascular conversion in age-related macular degeneration (AMD). Patient unidentified data aggregated by Vestrum Health, LLC (VH) from over 320 US retina specialists was analyzed to compare the conversion rate from dry to neovascular (wet) AMD in a practice employing VPT (VPT group) compared to those employing standard care alone (SCA group) between January 2017 through July 2023. 500,00 eyes were filtered then matched for neovascular conversion risk factors by propensity scoring and compared in a 10/1 ratio of 7370 SCA and 737 VPT treated eyes. SCA eyes had significantly fewer clinical encounters and shorter follow up than the VPT group. Despite this, the risk of neovascular conversion by PS was significantly lower in the VPT group compared to SCA (HR 5.73, p < 0.0001). Analysis matching the encounter frequency of both groups as a post-randomization variable produced a similar HR (HR 5.98, p < 0.0001). Because 9% of eyes in the VPT group were not treated with VPT due to bilateral early (low-risk) AMD, analysis comparing the SCA group to VPT-treated eyes was done that also showed significantly lower conversion rates in the VPT-treated eyes, with or without encounter frequency matching (HR 5.84, 5.65, p < 0.0001). Visual acuity was consistently better in VPT eyes compared to SCA eyes throughout the study time window. The advantage of VPT over SCA increased with increased SCA encounter frequency and higher conversion risk factors, including age and ICD10 coded dry AMD severity. Neovascular (wet) AMD is the main cause of irreversible visual loss worldwide. Consistent with two prior studies, the current study finds Vision Protection Therapy markedly more effective at both recognizing and preventing neovascular AMD than the current standard of care, benefiting the highest risk dry AMD eyes the most.
A new advance on dimensional-aware scalar, vector and matrix operations in C++
Authors: Stan Eduard George , Ciubotaru Dan Andrei , Renda Michele , Alexa Călin
Published: October 2023

We review the dimensional check problem of the high-level programming languages, discuss the existing solutions, and come up with a new solution suited for scientific and engineering computations. Then, we introduce , our library designed to make scalar, vector, and matrix operations using units of measurement. Moreover, supports dimensional-aware operations for complex numbers, quaternions, octonions, and sedenions. We provide tables of the relevant functions and operators implemented. Our library was compared with several existing solutions, and the results are shown in the performance section. Finally, we present our future plans for improving the current implementation.
The microbiome of African penguins (Spheniscus demersus) under managed care resembles that of wild marine mammals and birds
Authors: Graciette Ana G. Clavere , Hoopes Lisa A. , Clauss Tonya , Stewart Frank J. , Pratte Zoe A.
Published: October 2023

Animals under managed care in zoos and aquariums are ideal surrogate study subjects for endangered species that are difficult to obtain in the wild. We compared the fecal and oral microbiomes of healthy, managed African penguins (Spheniscus demersus) to those of other domestic and wild vertebrate hosts to determine how host identity, diet, and environment shape the penguin microbiome. The African penguin oral microbiome was more similar to that of piscivorous marine mammals, suggesting that diet and a marine environment together play a strong role in shaping the oral microbiome. Conversely, the penguin cloaca/fecal microbiome was more similar to that of other birds, suggesting that host phylogeny plays a significant role in shaping the gut microbiome. Although the penguins were born under managed care, they had a gut microbiome more similar to that of wild bird species compared to domesticated (factory-farmed) birds, suggesting that the managed care environment and diet resemble those experienced by wild birds. Finally, the microbiome composition at external body sites was broadly similar to that of the habitat, suggesting sharing of microbes between animals and their environment. Future studies should link these results to microbial functional capacity and host health, which will help inform conservation efforts.