bluuebunny/crossref_metadata_2025 huggingface dataset:
Generic symmetry defect set of an algebraic curve
Authors: Dias L. , Farnik M. , Jelonek Z.
Published: December 2023

Let

X
⊂

C

2
n

X \subset \mathbb {C}^{2n}

be an

n
n

-dimensional algebraic variety. We define the algebraic version of the generic symmetry defect set (Wigner caustic) of

X
X

. Moreover, we compute its singularities as well as degree, genus and Euler characteristic for

X
d

X_d

being a generic (smooth and transversal to the line at infinity) curve of degree

d
d

in 

C

2

\mathbb {C}^2

.
A Large-Scale Hydroponic Evaluation of Rice Mutants for Pythium Resistance
Authors: Syu Zun-Jie , Tu Chi-Kuan , Chen Chi-Yu , Lo Shuen-Fang , Lee Miin-Huey
Published: December 2023

Rice is a major staple crop worldwide. However, the occurrence of rice diseases during cultivation poses a significant challenge to achieving optimal yields. Among the major pathogens, Pythium species, which cause seedling blight, are of particular concern. Pythium infects rice roots through zoospores, mycelia, or oospores, leading to root rot, stunting, yellowing, and ultimately seedling damping-off. While many disease resistance-related genes have been reported in rice, only very limited research has been associated with resistance to Pythium infection. In this study, we aimed to establish a rapid screening system to identify rice lines that are resistant or susceptible to the Pythium pathogen in rice nurseries. We conducted evaluations on important factors, including virulence, inoculation method, seed-soaking period, and the measurement of disease severity. As a result, we successfully developed a screening system that allows for high-throughput and rapid screening of the Taiwan Rice Insertional Mutant (TRIM) library for mutant lines exhibiting resistance to P. arrhenomanes. Furthermore, we identified a slightly resistant TRIM line and explored potential genes encoding endoglucanase-1 precursor and malonyl-CoA decarboxylase that may be involved in conferring resistance to P. arrhenomanes.
Diagnosis of Malignant Pulmonary Nodules Using a Combination of Tumor-associated Autoantibodies and Computed Tomography
Authors: Liu Xiao , Shen Qing , Wen Yuchan , Jiang Zhijiao , Ma Zheng , Zeng Pinqiang , He Jian , Liao Yu , Huang Yong , Huang Jing
Published: December 2023

Background:

Diagnosis of malignant pulmonary nodules can greatly reduce the occurrence of lung cancer death, and computed tomography (CT) is commonly used in diagnosis. In addition, tumor-associated autoantibodies (TAAbs) show high specificity and stability. We aim to establish a computable risk model of pulmonary nodules by combining CT with TAAb detection.

Methods:

The concentrations of 7 TAAbs (p53, PGP9.5, SOX2, GAGE7, GBU4-5, CAGE, MAGEA1, and CAGE) were assayed using the enzyme-linked immunosorbent assay in 136 patients with pulmonary nodules (84 with newly diagnosed lung adenocarcinoma, 21 with squamous cell carcinoma, and 31 with benign nodules) and 42 control subjects without pulmonary nodules. We then drew receiver operating characteristic curves and conducted logistic regression to analyze the diagnostic efficiency of our method in the detection of lung cancer.

Results:

The positivity rate of the 7 TAAbs was 49.5%, and the specificity was 83.6%. Our regression results indicated 65% overall accuracy, 44.76% sensitivity, and 76.71% specificity. Notably, when combined with CT imaging and the demographic characteristics, diagnostic accuracy increased to 73.4%, sensitivity to 61.5%, and specificity to 87.1%. The positive predictive value and negative predictive value were 93% and 41%, respectively.

Conclusions:

Our study provides a method that combines 7 serum TAAbs with imaging and demographic characteristics to diagnose malignant pulmonary nodules more accurately than existing methods.
Characteristics and End-of-Life Care Pathways of Decedents From a National Cohort of Assisted Living Residents
Authors: Belanger Emmanuelle , Rosendaal Nicole , Wang Xiao (Joyce) , Teno Joan M. , Gozalo Pedro L. , Dosa David , Thomas Kali S.
Published: December 2023

Background:

Assisted living (AL) is an increasingly common, place of care for dying persons. However, it remains unclear to what extent residents are able to age in place or if AL represents an additional transition before death.

Objectives:

Examine the sociodemographic characteristics, comorbidities, health care utilization, and end-of-life care pathways of AL residents before death.

Research Design:

A national cohort study of fee-for-service Medicare beneficiaries residing in large AL communities (25+ beds) during the month of January 2017 with 3 years of follow-up, using administrative claims data.

Subjects:

268,812 AL residents.

Measures:

Sociodemographic characteristics, comorbidities, and health care utilization at the end of life.

Results:

Between 2017 and 2019, 35.1% of the study cohort died. Decedents were more likely than the overall AL population to be 85 years old or older (76.5% vs. 59.5%), and diagnosed with Alzheimer’s disease and related dementia (70.3% vs. 51.6%). Most decedents (96.2%) had some presence in AL during the last year of life, but over 1 in 5 left AL before the last month of life. Among those in AL on day 30 before death, nearly half (46.4%) died in place without any health care transition, while 13.2% had 3 or more transfers before dying.

Conclusions:

AL is an important place of care for dying persons, especially for those with dementia. These findings indicate a need to assess existing policies and processes guiding the care of the frail and vulnerable population of dying AL residents.
Multimodality Therapy, Followed by Laparoscopic Gastrectomy, for Unresectable Gastric Cancer With Outlet Obstruction and Bulky N2 Metastases
Authors: Ma Liangang , Zhao Baocheng , Zhang Yudong , Jing Shuai , Qu Hao
Published: December 2023

Background:

Patients who have gastric cancer with outlet obstruction (GCOO) and bulky N2 metastases cannot undergo curative resection and tolerate chemotherapy poorly, which may be improved by multimodality therapy (MMT) combined with laparoscopic gastrectomy.

Patients and Methods:

The records of patients with GCOO and bulky N2 metastases who received MMT including nasojejunal feeding combined with preoperative chemotherapy (PCT), followed by laparoscopic exploration [enteral nutritional (EN) group] in sequence or laparoscopic gastrojejunostomy (LGJ) before PCT plus laparoscopic gastrectomy (LGJ group) were retrospectively reviewed. Prognostic Nutritional Index, gastric outlet obstruction scoring system grade, quality of life, response to PCT, surgical outcomes, and long-term survival were analyzed.

Results:

Fifty-four consecutive patients with GCOO and bulky N2 metastases were identified. The Prognostic Nutritional Index and Nutritional Risk Screening-2002 score of patients were significantly improved as a result of multimodal therapy, but no superiority was demonstrated between the EN group and the LGJ group. The quality of life (52.6 ± 11.4 vs 68.2 ± 13.5, P = 0.036) and gastric outlet obstruction scoring system (P < 0.05) of patients in the LGJ group were better compared with the EN group. The rate of laparoscopic D2 gastrectomy (94.3% vs 92.9%, P = 0.64) and R0 resection (91.4% vs 92.9%, P = 0.53) in the EN group was similar to the LGJ group. There were no significant differences for the 5-year overall survival rate (63.2% vs 57.1, P = 0.86) and the 5-year relapse-free survival rate (42.9% vs 53.8%, P = 0.54) of patients in the EN group compared with the LGJ group.

Conclusions:

MMT including EN support or laparoscopic gastrojejunostomy followed by laparoscopic D2 gastrectomy is a feasible and effective treatment for patients with GCOO and bulky N2 metastases.
High throughput screening identifies broad-spectrum Coronavirus entry inhibitors
Authors: Khan Suman , Partuk Efrat Ozer , Chiaravalli Jeanne , Kozer Noga , Shurrush Khriesto A. , Elbaz-Alon Yael , Scher Nadav , Giraud Emilie , Tran-Rajau Jaouen , Agou Fabrice , Barr Haim Michael , Avinoam Ori
Published: December 2023

The Covid-19 pandemic highlighted the pressing need for antiviral therapeutics capable of mitigating infection and spread of emerging coronaviruses (CoVs). A promising therapeutic strategy lies in inhibiting viral entry mediated by the Spike (S) glycoprotein. To identify small molecule inhibitors that block entry downstream of receptor binding, we established a high-throughput screening (HTS) platform based on pseudoviruses. We employed a three-step process to screen nearly 200,000 small molecules. First, we identified potential inhibitors by assessing their ability to inhibit pseudoviruses bearing the SARS-CoV-2 S glycoprotein. Subsequent counter-screening against pseudoviruses with the Vesicular Stomatitis Virus glycoprotein (VSV-G), yielding sixty-five SARS-CoV-2 S-specific inhibitors. These were further tested against pseudoviruses bearing the MERS-CoV S glycoprotein, which uses a different receptor. Out of these, five compounds including the known broad-spectrum inhibitor Nafamostat, were subjected to further validation and tested them against pseudoviruses bearing the S glycoprotein of the alpha, delta, and omicron variants as well as againstbona fideSARS-CoV-2in vitro. This rigorous approach revealed a novel inhibitor and its derivative as a potential broad-spectrum antiviral. These results validate the HTS platform and set the stage for lead optimization and future pre-clinical,in vivostudies.
Identification of a P62-TIF-IA axis that drives nucleolar fusion and the senescence associated secretory phenotype
Authors: Thoms Hazel C , Brant Tyler , Duckett Katie , Yang Yizheng , Dong Jinxi , Wang Hongfei , Derby Freya , Akeke Tumi , Mann Derek , Millar Fraser R , Kriegsheim Alex Von , Acosta Juan Carlos , Oakley Fiona , Stark Lesley A
Published: December 2023

Two key characteristics of senescent cells are nucleolar fusion and secretion of a plethora of pro-inflammatory cytokines called the senescence-associated secretory phenotype (SASP). The SASP is dependent on NF-κB but the initial trigger, and links with nucleoli, are unclear. Using multiplein vitroandin vivomodels, we show that an early response to oncogene- and therapy-induced senescence (OIS and TIS) is nuclear/nucleolar accumulation of the PolI complex component, TIF-IA. This accumulation is essential for nucleolar fusion, the SASP and senescence, independent of rDNA transcription. We show that in steady state, TIF-IA is targeted for autophagic degradation by the p62 cargo receptor and that accumulation in senescence occurs as a consequence of ATM activation, which disrupts the p62-TIF-IA interaction. In mice, TIF-IA accumulates in colonic mucosa with age, which is further enhanced in thenfkb1-/-model of accelerated ageing. Together, these results reveal a p62-TIF-IA nucleolar stress axis that regulates the SASP and senescence, and that warrants further investigation as an anti-ageing target.
The intrinsically disordered tail of ESCO1 binds DNA in a charge-dependent manner
Authors: Schoen Jeffrey R. , Chen Jingrong , Rankin Susannah
Published: December 2023

ESCO1 is an acetyltransferase enzyme that regulates chromosome organization and gene expression. It does this by modifying the Smc3 subunit of the Cohesin complex. Although ESCO1 is enriched at the base of chromatin loops in a Cohesin-dependent manner, precisely how it interacts with chromatin is unknown. Here we show that the basic and intrinsically disordered tail of ESCO1 binds DNA with very high affinity, likely through electrostatic interaction. We show that neutralization of positive residues in the N-tail reduces both DNA binding in vitro and association of the enzyme with chromatin in cells. Additionally, disruption of the chromatin state and charge distribution reduces chromatin bound ESCO1. Strikingly, defects in DNA binding do not affect total SMC3 acetylation or sister chromatid cohesion, suggesting that ESCO1-dependent acetylation can occur independently of direct chromatin association. We conclude that the intrinsically disordered tail of ESCO1 binds DNA with both high affinity and turnover, but surprisingly, ESCO1 catalytic activity occurs independently of direct DNA binding by the enzyme.
DRR pioneers interview with Andrew Maskrey and Allan Lavell
Authors: Maskrey Andrew , Lavell Allan
Published: December 2023

Purpose

The interview traces the early discussions in the context of disasters as developmental failures.

Design/methodology/approach

The transcript and video was developed in the context of a United Nations Office for Disaster Risk Reduction (UNDRR) project on the history of DRR.

Findings

The interview traces the development of disaster risk reduction discussions in different contexts such as “LA RED” network in Latin America.

Originality/value

The interview clearly highlights the need to not forget the early thoughts on vulnerability and disaster risk.
Integrated trophic position as a proxy for food‐web complexity
Authors: Ishikawa Naoto F. , Takashima Ayaka , Maruoka Hirokazu , Kondoh Michio
Published: December 2023

There are two distinct approaches to describing the distributions of biomass and species in food webs: one to consider them as discrete trophic levels (TLs); and the other to consider them as continuous trophic positions (TPs). Bridging the gap between these two perspectives presents a nontrivial challenge in integrating biodiversity and food‐web structure.

Food network unfolding (FNU) is a technique used to bridge this gap by partitioning the biomass of species into integer TLs to compute three complexity indices, namely vertical (DV), horizontal (DH) and range (DR) diversity (D indices), through decomposition of Shannon's index H′. Using FNU, the food web (a network of species with unique TPs) is converted to a linear food chain (a biomass distribution at discrete TLs). This enables us to expect that the unfolded biomass within species decreases exponentially as the TL increases. Under this condition, the mean TL value in unfolded food chains is hypothesized to have an exponential relationship with the vertical diversity, DV. To explore this, we implemented FNU and calculated D indices for food webs publicly available at EcoBase (n = 158) and calculated the integrated TP (iTP), defined as the biomass‐weighted average TP of a given food web. The iTP corresponds to the mean TL in unfolded food chains and can be empirically measured through compound‐specific isotope analysis of amino acids (CSIA‐AA).

Although our analysis is biased towards marine ecosystems, we revealed an exponential relationship between iTP and DV, suggesting that iTP can serve as a measurable proxy for DV. Furthermore, we found a positive correlation between the iTP observed in the total communities (total iTP) and the iTPs of partial communities consisting only of species with 2.0 ≤ TP < 3.0 (partial iTP; r2 = 0.48), suggesting that DV can be predicted using partial iTP.

Our findings suggest that the net effect of species diversity, excluding the effect of biomass (corresponding to H′ − DV), on food‐web complexity can be revealed by combining CSIA‐AA with biodiversity analysis (e.g. environmental DNA).
Lacosamide use during breastfeeding: A case report and a literature review
Authors: Cercos Morgan , Seqat Ines , Facile Anthony , Vial Thierry , Auffret Marine
Published: December 2023

Lacosamide, a voltage‐gated sodium channel inhibitor, is an anti‐seizure medication (ASM) from the age of 4. We report on the case of a woman treated with lacosamide for pharmacoresistant epilepsy who breastfed her infant for more than 6 months after birth. The infant's blood concentrations of lacosamide were 2.4 mg/L on Day 1 and less than 1 mg/L on Day 10 (reference values are 1–10 mg/L). No adverse drug reactions (ADRs) were reported for the infant. Eight cases of breastfeeding by mothers receiving lacosamide are described in the literature. These data confirm that a significant amount of lacosamide seems to pass into breast milk, with a relative infant dose (RID) above 20% in two cases but a low RID (1.8%) in another case. Nevertheless, blood tests, performed in two breastfed infants, revealed low concentrations of lacosamide. No ADRs were reported in eight of the breastfed infants; however, one infant, whose mother was also treated with levetiracetam, presented poor feeding and sleepiness at Day 15 of life. Given the well‐known benefits of breastfeeding for both mothers and their infants, as well as the above reassuring data, breastfeeding of healthy full‐term infants could be possible for mothers on lacosamide monotherapy. Nonetheless, relatives should be warned that data concerning the safety of lacosamide during breastfeeding are scarce and that long‐term neurodevelopment outcomes in breastfed children are unknown. Clinical monitoring of breastfed infants for drowsiness, adequate weight gain, or cutaneous rash is recommended. Additionally, the infants' serum levels should be measured in case of an unexplained adverse reaction.
Preparation and enhanced mechanical properties of novel Al2O3‐C ceramic filter reinforced by microporous powder and SiC whiskers
Authors: Yan Wen , Chen Zhe , Li Guangqiang , Hong Shaosong , Li Nan
Published: December 2023

In present work, the novel Al2O3‐C ceramic filter fabricated by using microporous corundum‐spinel powder instead of dense Al2O3 powder and reinforced by SiC whiskers is proposed. The effects of Si powder content (0, 3, 6, and 9 wt. %) on the microstructures and mechanical properties of the filters were studied. After replacing the α‐Al2O3 micro‐powder with microporous corundum‐spinel powder, the in situ spinel whiskers were formed inside the filter skeleton under the reducing atmosphere. The rough surface structure of the microporous powder increased the interface contact area with the small‐sized carbon particles, resulting in a compact interface bonding in the filter skeleton and a higher cold compressive strength of the filter. When the Si powder content increased to 6–9 wt. %, the in‐situ SiC whiskers were formed not only between the microporous powder, but also inside the pores near the surface of it by vapor‐solid reaction mechanism in the filter skeleton. The SiC whiskers synergized with the microporous powder to form a more compact interface structure, thus remarkably enhancing their cold compressive strength and thermal shock resistance. Overall, the mechanical properties of the filters were significantly improved by the addition of 9 wt. % Si powder. The filter skeleton had an apparent porosity of 36.2% and a bulk density of 1.93 g/cm3. The filter also exhibited a high cold compressive strength of 1.59 MPa and a superior thermal shock resistance. It has the potential for better purification efficiency on molten steel in the future due to a rougher skeleton surface structure compared to existing Al2O3‐C filters.
The effect of Dendrobium officinale extract in inhibiting the senescence of H2O2‐induced fibroblasts based on the senescence‐associated secretory phenotype
Authors: Li Lingyu , Zhu Le , Chen Mo , Zhao Ya , Jia Haidong
Published: December 2023

Background

Dendrobium officinale is widely used for a long time in China, with effect of antioxidation, antitumor, enhancing immunity and so on. In recent years, Dendrobium officinale has been gradually used in cosmetics due to its powerful beauty effects.

Aims

Based on senescence‐associated secretory phenotype (SASP), we studied the antiaging effect of Dendrobium officinale extract (DOE) on skin.

Methods

The senescent model of human skin fibroblasts was established by the induction of H2O2, and the content of SASP factors was tested after the treatment of DOE, such as interleukin‐6 (IL‐6), monocyte chemoattractant protein‐1 (MCP‐1) and matrix metalloproteinase‐1 (MMP‐1).

Results

It was found that after the treatment with different concentrations of DOE, the contents of IL‐6, MCP‐1 and MMP‐1 all decreased in different degrees.

Conclusions

It indicated that DOE could inhibit the secretion of SASP factors and was a promising natural antiaging agent.
Assessing the relationship between census tract rurality and severe maternal morbidity in California (1997‐2018)
Authors: Berkowitz Rachel L. , Kan Peiyi , Gao Xing , Hailu Elleni M. , Board Christine , Lyndon Audrey , Mujahid Mahasin , Carmichael Suzan L.
Published: December 2023

Purpose

Recent studies have demonstrated an increased risk of severe maternal morbidity (SMM) for people living in rural versus urban counties. Studies have not considered rurality at the more nuanced subcounty census‐tract level. This study assessed the relationship between census‐tract‐level rurality and SMM for birthing people in California.

Methods

We used linked vital statistics and hospital discharge records for births between 1997 and 2018 in California. SMM was defined by at least 1 of 21 potentially fatal conditions and lifesaving procedures. Rural‐Urban Commuting Area codes were used to characterize census tract rurality dichotomously (2‐category) and at 4 levels (4‐category). Covariates included sociocultural‐demographic, pregnancy‐related, and neighborhood‐level factors. We ran a series of mixed‐effects logistic regression models with tract‐level clustering, reporting risk ratios and 95% confidence intervals (CIs). We used the STROBE reporting guidelines.

Findings

Of 10,091,415 births, 1.1% had SMM. Overall, 94.3% of participants resided in urban/metropolitan and 5.7% in rural tracts (3.9% micropolitan, 0.9% small town, 0.8% rural). In 2‐category models, the risk of SMM was 10% higher for birthing people in rural versus urban tracts (95% CI: 6%, 13%). In 4‐category models, the risk of SMM was 16% higher in micropolitan versus metropolitan tracts (95% CI: 12%, 21%).

Conclusion

The observed rurality and SMM relationship was driven by living in a micropolitan versus metropolitan tract. Increased risk may result from resource access inequities within suburban areas. Our findings demonstrate the importance of considering rurality at a subcounty level to understand locality‐related inequities in the risk of SMM.
Information and Confrontation in Legislative Oversight
Authors: Eldes Ayse , Fong Christian , Lowande Kenneth
Published: December 2023

Committees can use oversight hearings to collect and communicate the information Congress needs to oversee the bureaucracy, but many worry that members instead focus on scoring political points by lambasting witnesses. We leverage the collective judgment of congressional staff to measure how exchanges between legislators and witnesses vary on two separable dimensions: information and confrontation. Contrary to the conventional wisdom that confrontation crowds out information, we show that members of the president's party engage in less confrontational oversight and reveal no more or less information than their peers.
Introduction
Authors: Onder E. Nihan
Published: December 2023

In the design and operation of nuclear reactors, a concept, called defence-in-depth, is applied to establish a series of levels of defence. The general objective of defence-in-depth is to ensure that a single failure at one level of defence would not propagate to jeopardize defence-in-depth at subsequent levels. There are five levels of defence-in-depth in the concept of nuclear power plant (NPP): Level 1 - Prevention of abnormal operation and failures; Level 2 - Control of abnormal operation and detection of failures; Level 3 - Control of accidents within the design basis; Level 4 - Control of severe plant conditions, including prevention of accident progression and mitigation of the consequences of severe accidents; Level 5 - Mitigation of radiological consequences of significant releases of radioactive materials.
College Football “Kids”: Infantilizing Language in Football Bowl Subdivision Bowl Game Broadcasts
Authors: Corr Chris , Southall Crystal , Hawkins Billy , Southall Richard M.
Published: December 2023

Paternalistic institutional structures are strategically arranged to maintain locus of control and preserve male-centric patriarchal authority. A confluence of cultural, social, and legal structures perpetuates paternalism within National Collegiate Athletic Association college sport and specifically in Football Bowl Subdivision (FBS) football. This study examined FBS bowl game broadcasts to determine the prevalence of paternalistic and infantilizing commentary. An analysis of in-game commentary from a sample of 18 FBS bowl games from the 2019 to 2020 season revealed that commentators frequently infantilize FBS football players, normalizing a paternalistic and exploitative coach–athlete relationship.
Bacterial denitrification drives elevated N
2
O emissions in arid southern California drylands
Authors: Krichels Alexander H. , Jenerette G. Darrel , Shulman Hannah , Piper Stephanie , Greene Aral C. , Andrews Holly M. , Botthoff Jon , Sickman James O. , Aronson Emma L. , Homyak Peter M.
Published: December 2023

Soils are the largest source of atmospheric nitrous oxide (N
2
O), a powerful greenhouse gas. Dry soils rarely harbor anoxic conditions to favor denitrification, the predominant N
2
O-producing process, yet, among the largest N
2
O emissions have been measured after wetting summer-dry desert soils, raising the question: Can denitrifiers endure extreme drought and produce N
2
O immediately after rainfall? Using isotopic and molecular approaches in a California desert, we found that denitrifiers produced N
2
O within 15 minutes of wetting dry soils (site preference = 12.8 ± 3.92 per mil, δ
15
N
bulk
= 18.6 ± 11.1 per mil). Consistent with this finding, we detected nitrate-reducing transcripts in dry soils and found that inhibiting microbial activity decreased N
2
O emissions by 59%. Our results suggest that despite extreme environmental conditions—months without precipitation, soil temperatures of ≥40°C, and gravimetric soil water content of <1%—bacterial denitrifiers can account for most of the N
2
O emitted when dry soils are wetted.
Ex vivo tissue perturbations coupled to single-cell RNA-seq reveal multilineage cell circuit dynamics in human lung fibrogenesis
Authors: Lang Niklas J. , Gote-Schniering Janine , Porras-Gonzalez Diana , Yang Lin , De Sadeleer Laurens J. , Jentzsch R. Christoph , Shitov Vladimir A. , Zhou Shuhong , Ansari Meshal , Agami Ahmed , Mayr Christoph H. , Hooshiar Kashani Baharak , Chen Yuexin , Heumos Lukas , Pestoni Jeanine C. , Molnar Eszter Sarolta , Geeraerts Emiel , Anquetil Vincent , Saniere Laurent , Wögrath Melanie , Gerckens Michael , Lehmann Mareike , Yildirim Ali Önder , Hatz Rudolf , Kneidinger Nikolaus , Behr Jürgen , Wuyts Wim A. , Stoleriu Mircea-Gabriel , Luecken Malte D. , Theis Fabian J. , Burgstaller Gerald , Schiller Herbert B.
Published: December 2023

Pulmonary fibrosis develops as a consequence of failed regeneration after injury. Analyzing mechanisms of regeneration and fibrogenesis directly in human tissue has been hampered by the lack of organotypic models and analytical techniques. In this work, we coupled ex vivo cytokine and drug perturbations of human precision-cut lung slices (hPCLS) with single-cell RNA sequencing and induced a multilineage circuit of fibrogenic cell states in hPCLS. We showed that these cell states were highly similar to the in vivo cell circuit in a multicohort lung cell atlas from patients with pulmonary fibrosis. Using micro-CT–staged patient tissues, we characterized the appearance and interaction of myofibroblasts, an ectopic endothelial cell state, and basaloid epithelial cells in the thickened alveolar septum of early-stage lung fibrosis. Induction of these states in the hPCLS model provided evidence that the basaloid cell state was derived from alveolar type 2 cells, whereas the ectopic endothelial cell state emerged from capillary cell plasticity. Cell-cell communication routes in patients were largely conserved in hPCLS, and antifibrotic drug treatments showed highly cell type–specific effects. Our work provides an experimental framework for perturbational single-cell genomics directly in human lung tissue that enables analysis of tissue homeostasis, regeneration, and pathology. We further demonstrate that hPCLS offer an avenue for scalable, high-resolution drug testing to accelerate antifibrotic drug development and translation.
Phosphate-related genomic islands as drivers of environmental adaptation in the streamlined marine alphaproteobacterial HIMB59
Authors: Molina-Pardines Carmen , Haro-Moreno Jose M. , López-Pérez Mario
Published: December 2023

Prokaryotic species are composed of multiple clonal lineages coexisting in the same habitat. In recent years, understanding the maintenance of this high intraspecific genetic diversity in asexual microorganisms has been a challenge for microbial ecology. In this study, we investigated the potential ecological role of this genomic heterogeneity in the marine HIMB59 clade. The metagenomic recruitment revealed the presence of three main genomospecies with different ecological distribution patterns within the two defined families. Genomic analysis revealed the presence of a flexible genomic island conserved throughout the order at the same position in the genome and related to phosphate (P) metabolism. The different versions of this island showed a distribution correlated with the concentration of P in the environment but not with the phylogeny at the genomospecies level. At high P availability (>0.5 µM), HIMB59 cells had only the high-affinity phosphate transporter operon (PstSCAB and PhoU). Under conditions of higher P scarcity (<0.05 µM), the cells presented a higher number of genes for the acquisition of P groups from other sources such as organic molecules and their storage. Additionally, in oligotrophic regions exhibiting extreme P depletion, such as the Mediterranean Sea, we found a second flexible genomic island related to phosphonate catabolism to supply metabolic P requirements. These results suggest that these microbes maintain in natural populations a gene pool with an equivalent biological function that allows them to respond to variations in certain micronutrients, creating ecologically distinct lineages within each species.

IMPORTANCE

These results shed light on the evolutionary strategies of microbes with streamlined genomes to adapt and survive in the oligotrophic conditions that dominate the surface waters of the global ocean. At the individual level, these microbes have been subjected to evolutionary constraints that have led to a more efficient use of nutrients, removing non-essential genes named as “streamlining theory.” However, at the population level, they conserve a highly diverse gene pool in flexible genomic islands resulting in polyclonal populations on the same genomic background as an evolutionary response to environmental pressures. Localization of these islands at equivalent positions in the genome facilitates horizontal transfer between clonal lineages. This high level of environmental genomic heterogeneity could explain their cosmopolitan distribution. In the case of the order HIMB59 within the class
Alphaproteobacteria
, two factors exert evolutionary pressure and determine this intraspecific diversity: phages and the concentration of P in the environment.
Supplemental Material: Constraints of boron and oxygen stable isotopes on dehydration fluids, sediment-derived melts, and crustal assimilation of the Toba volcanic system (Indonesia)
Authors: Liu  , al. et
Published: December 2023

Detailed description of the analytical methods, Figure S1, and Tables S1–S3. 
Effectiveness of conservative management versus laparoscopic cholecystectomy in the prevention of recurrent symptoms and complications in adults with uncomplicated symptomatic gallstone disease (C-GALL trial): pragmatic, multicentre randomised controlled trial
Authors: Ahmed Irfan , Hudson Jemma , Innes Karen , Hernández Rodolfo , Gillies Katie , Bruce Rebecca , Bell Victoria , Avenell Alison , Blazeby Jane , Brazzelli Miriam , Cotton Seonaidh , Croal Bernard , Forrest Mark , MacLennan Graeme , Murchie Peter , Wileman Samantha , Ramsay Craig
Published: December 2023

Objective

To assess the clinical and cost effectiveness of conservative management compared with laparoscopic cholecystectomy for the prevention of symptoms and complications in adults with uncomplicated symptomatic gallstone disease.

Design

Parallel group, pragmatic randomised, superiority trial.

Setting

20 secondary care centres in the UK.

Participants

434 adults (>18 years) with uncomplicated symptomatic gallstone disease referred to secondary care, assessed for eligibility between August 2016 and November 2019, and randomly assigned (1:1) to receive conservative management or laparoscopic cholecystectomy.

Interventions

Conservative management or surgical removal of the gallbladder.

Main outcome measures

The primary patient outcome was quality of life, measured by area under the curve, over 18 months using the short form 36 (SF-36) bodily pain domain, with higher scores (range 0-100) indicating better quality of life. Other outcomes included costs to the NHS, quality adjusted life years (QALYs), and incremental cost effectiveness ratio.

Results

Of 2667 patients assessed for eligibility, 434 were randomised: 217 to the conservative management group and 217 to the laparoscopic cholecystectomy group. By 18 months, 54 (25%) participants in the conservative management arm and 146 (67%) in the cholecystectomy arm had received surgery. The mean SF-36 norm based bodily pain score was 49.4 (standard deviation 11.7) in the conservative management arm and 50.4 (11.6) in the cholecystectomy arm. The SF-36 bodily pain area under the curve up to 18 months did not differ (mean difference 0.0, 95% confidence interval −1.7 to 1.7; P=1.00). Conservative management was less costly (mean difference −£1033, (−$1334; −€1205), 95% credible interval −£1413 to −£632) and QALYs did not differ (mean difference −0.019, 95% credible interval −0.06 to 0.02).

Conclusions

In the short term (≤18 months), laparoscopic surgery is no more effective than conservative management for adults with uncomplicated symptomatic gallstone disease, and as such conservative management should be considered as an alternative to surgery. From an NHS perspective, conservative management may be cost effective for uncomplicated symptomatic gallstone disease. As costs, complications, and benefits will continue to be incurred in both groups beyond 18 months, future research should focus on longer term follow-up to establish effectiveness and lifetime cost effectiveness and to identify the cohort of patients who should be routinely offered surgery.

Trial registration

ISRCTN registry
ISRCTN55215960
.
Age at menarche, type 2 diabetes and cardiovascular disease complications in US women aged under 65 years: NHANES 1999–2018
Authors: Santos Maria P , Li Yaling , Bazzano Lydia A , He Jiang , Rexrode Kathryn M , Ley Sylvia H
Published: December 2023

Background

Diabetes and diabetes complications are on the rise in US adults aged <65 years, while onset of menarche at a younger age is also increasing. We examined the associations of age at menarche with type 2 diabetes among women aged <65 years and with cardiovascular disease (CVD) complications among women with diabetes.

Methods

Using the nationally representative cross-sectional National Health and Nutrition Examination Survey 1999–2018, women aged 20–65 years free of cancer were included in the current analysis. Diabetes was defined as a self-reported diabetes diagnosis. CVD was defined as coronary heart disease or stroke. Age at menarche was self-reported age of first menstruation and categorised into ≤10, 11, 12, 13, 14 and ≥15 years.

Results

Of 17 377 women included in the analysis, 1773 (10.2%) reported having type 2 diabetes. Earlier age at menarche was associated with type 2 diabetes compared with median age at menarche of 13 years, after adjustment for age, race/ethnicity, education, parity, menopause status and family history of diabetes, smoking status, physical activity, alcohol consumption and body mass index (p for trend=0.02). Among women with diabetes, earlier age at menarche was associated with stroke with similar adjustment (p for trend=0.03), but not with total CVD. Extremely early age at menarche (≤10 years) was significantly associated with stroke (adjusted OR 2.66 (95% CI 1.07 to 6.64)) among women aged <65 years with diabetes with similar adjustment.

Conclusions

Earlier age at menarche was associated with type 2 diabetes among young and middle-aged women in the USA and with stroke complications among these women living with diabetes.
Clinical impacts of an integrated electronic health record-based smoking cessation intervention during hospitalisation
Authors: Banerjee Somalee , Alabaster Amy , Adams Alyce S , Fogelberg Renee , Patel Nihar , Young-Wolff Kelly
Published: December 2023

Objective

To assess the effects of an electronic health record (EHR) intervention that prompts the clinician to prescribe nicotine replacement therapy (NRT) at hospital admission and discharge in a large integrated health system.

Design

Retrospective cohort study using interrupted time series (ITS) analysis leveraging EHR data generated before and after implementation of the 2015 EHR-based intervention.

Setting

Kaiser Permanente Northern California, a large integrated health system with 4.2 million members.

Participants

Current smokers aged ≥18 hospitalised for any reason.

Exposure

EHR-based clinical decision supports that prompted the clinician to order NRT on hospital admission (implemented February 2015) and discharge (implemented September 2015).

Main outcomes and measures

Primary outcomes included the monthly percentage of admitted smokers with NRT orders during admission and at discharge. A secondary outcome assessed patient quit rates within 30 days of hospital discharge as reported during discharge follow-up outpatient visits.

Results

The percentage of admissions with NRT orders increased from 29.9% in the year preceding the intervention to 78.1% in the year following (41.8% change, 95% CI 38.6% to 44.9%) after implementation of the admission hard-stop intervention compared with the baseline trend (ITS estimate). The percentage of discharges with NRT orders increased acutely at the time of both interventions (admission intervention ITS estimate 15.5%, 95% CI 11% to 20%; discharge intervention ITS estimate 13.4%, 95% CI 9.1% to 17.7%). Following the implementation of the discharge intervention, there was a small increase in patient-reported quit rates (ITS estimate 5.0%, 95% CI 2.2% to 7.8%).

Conclusions

An EHR-based clinical decision-making support embedded into admission and discharge documentation was associated with an increase in NRT prescriptions and improvement in quit rates. Similar systemic EHR interventions can help improve smoking cessation efforts after hospitalisation.
Effect of synchronous remote-based interventions on suicidal behaviours: protocol for a systematic review and meta-analysis
Authors: Comendador Laura , Jiménez-Villamizar María Paola , Losilla Josep-Maria , Sanabria-Mazo Juan P , Mateo-Canedo Corel , Cebrià Ana Isabel , Sanz Antoni , Palao Diego J
Published: December 2023

Introduction

Suicide is among the leading causes of preventable death worldwide. The impact of suicide affects the personal, social and economic levels. Therefore, its prevention is a priority for public health systems. Previous studies seem to support the efficacy of providing active contact to people who have made a suicide attempt. The current systematic review and meta-analysis aims to investigate the efficacy of distance suicide prevention strategies implemented through synchronous technology-based interventions.

Methods and analysis

This protocol is designed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. The bibliographical searches were conducted in the databases PubMed, PsycINFO, Scopus and Web of Science in April 2022, with no restrictions on the time of publication and limited to publications in English or Spanish. The search strategy was performed using free-text terms and Medical Subject Headings terms: suicide, follow-up, synchronous, remote, telehealth, telephone, hotline, video-conference and text message. Two reviewers will independently conduct study screening, selection process, data extraction and risk of bias assessment. The analysis and synthesis of the results will be both qualitative and quantitative. A narrative synthesis, presented in a comprehensive table, will be performed and meta-analysis will be conducted, as appropriate, if sufficient data are provided.

Ethics and dissemination

The present review and meta-analysis will not require ethical approval, as it will use data collected from previously published primary studies. The findings of this review will be published in peer-reviewed journals and widely disseminated.

PROSPERO registration number

CRD42021275044.
Estimating the frequency of inpatient adverse events using a two-step retrospective chart review: a study protocol
Authors: ul Hassan Syed Sabih , Asif Fozia , Haque Ghazal , Ayub Farwa , Munir Tahir , Khan Fauzia , Siddiqi Sameen , Latif Asad
Published: December 2023

Introduction

Adverse events are a major cause of patient harm in the hospitalised setting. Low-income and middle-income countries account for a disproportionate share of the global burden of adverse events. However, patient safety research is still centred around high-income countries and high-resource health systems. The methods and data produced from these efforts are ill-suited to low-income and middle-income systems due to the social and technical differences between these settings. We aim to use our pilot-tested, locally developed methodology to estimate the frequency and characteristics of adverse events in hospitalised patients in a lower-middle-income country to inform patient safety policies and initiatives.

Methods and analysis

This multi-centre study will employ a two-step chart review methodology to identify adverse events in a representative sample of patients admitted at five hospitals between 1 January 2019 and 31 December 2019. The first step will include assessing patient files against a list of triggers to detect adverse events and the second step will involve an in-depth review of the events to capture pertinent characteristics. The triggers have been adapted from validated tools used in other studies. The reviewing team will be trained on the use of research tools and operational definitions to ensure that data are collected uniformly. The main outcome of interest is the rate at which adverse events occur in hospitalised patients. Further analysis will look to identify and quantify associations between the main outcome of interest and a variety of variables such as patient age and gender using tests of independence and regression techniques.

Ethics and dissemination

This study protocol has been approved by the Ethics Review Committee at Aga Khan University (Reference number: 2023-6324-24566). The findings of this study will be published in a peer-reviewed journal and disseminated to the public through national and international conferences, workshops, websites and social media.
Efficacy of pharmacological interventions: a systematic review informing the 2023 EULAR recommendations for the management of fatigue in people with inflammatory rheumatic and musculoskeletal diseases
Authors: Farisogullari Bayram , Santos Eduardo José Ferreira , Dures Emma , Geenen Rinie , Machado Pedro M
Published: December 2023

Objective

To identify the best evidence on the efficacy of pharmacological interventions in reducing fatigue in people with inflammatory rheumatic and musculoskeletal diseases (I-RMDs) and to summarise their safety in the identified studies to inform European Alliance of Associations for Rheumatology recommendations for the management of fatigue in people with I-RMDs.

Methods

Systematic review of adults with I-RMDs conducted according to the Cochrane Handbook. Search strategy ran in Medline, Embase, Cochrane Library, CINAHL Complete, PEDro, OTseeker and PsycINFO. Only randomised controlled trials (RCTs) or controlled clinical trials were eligible. Assessment of risk of bias, data extraction and synthesis performed by two reviewers independently and in duplicate. Data pooled in statistical meta-analyses.

Results

From 4151 records, 455 were selected for full-text review, 99 fulfilled the inclusion criteria and 19 RCTs were included in meta-analyses. Adalimumab was superior to placebo in reducing fatigue at 12 and 52 weeks in rheumatoid arthritis (RA) (n=3 and 2 RCTs; mean difference (MD)= −3.03, p<0.001; MD=−2.25, p=0.03, respectively). Golimumab (n=2 RCTs; 24 weeks: MD=−5.27, p<0.001), baricitinib (n=2 RCTs; 24 weeks: MD=−4.06, p<0.001), sarilumab (n=2 RCTs; 24 weeks: MD=−3.15, p<0.001), tocilizumab (n=3 RCTs; 24 weeks: MD=−3.69, p<0.001) and tofacitinib (n=3 RCTs; 12 weeks: MD=−4.44, p<0.001) were also superior to placebo in reducing fatigue in RA. A dose/effect relationship was observed for sarilumab, tocilizumab and tofacitinib. In spondyloarthritis (excluding psoriatic arthritis), secukinumab was superior to placebo in reducing fatigue at 16 weeks (n=2 RCTs; MD=−4.15, p<0.001), with a dose/effect relationship also observed. The narrative results of the RCTs not included in the meta-analysis indicated that several other pharmacological interventions were efficacious in reducing fatigue, with reassuring safety results.

Conclusions

Several pharmacological interventions are efficacious and generally safe for managing fatigue in people with I-RMDs.
On a New Stochastic Space of Solution for the Volterra-Type Summable Equations of Fuzzy Functions
Authors: Mohammed Mustafa M. , Bakery Awad A.
Published: December 2023

This article explains the sufficient requirements for a newly constructed stochastic space by Poisson-like matrices and weighted variable exponent sequence spaces of fuzzy functions, as well as the ideals of their operators, for the Kannan contraction operator to have a unique fixed point. Moreover, we investigate some examples and the numerous applications of solutions to Volterra-type summable equations of fuzzy functions.