bluuebunny/crossref_metadata_2025 huggingface dataset:
CohortFinder: an open-source tool for data-driven partitioning of digital pathology and imaging cohorts to yield robust machine-learning models
Authors: Fan Fan , Martinez Georgia , DeSilvio Thomas , Shin John , Chen Yijiang , Jacobs Jackson , Wang Bangchen , Ozeki Takaya , Lafarge Maxime W. , Koelzer Viktor H. , Barisoni Laura , Madabhushi Anant , Viswanath Satish E. , Janowczyk Andrew
Published: July 2024

Batch effects (BEs) refer to systematic technical differences in data collection unrelated to biological variations whose noise is shown to negatively impact machine learning (ML) model generalizability. Here we release CohortFinder (http://cohortfinder.com), an open-source tool aimed at mitigating BEs via data-driven cohort partitioning. We demonstrate CohortFinder improves ML model performance in downstream digital pathology and medical image processing tasks. CohortFinder is freely available for download at cohortfinder.com.
Cross-species transmission of Cryptosporidium in wild rodents from the southern region of Zhejiang Province of China and its possible impact on public health
Authors: Jiang Yanyan , Jiang Aiying , Ren Guangxu , Wang Long , Xin Xianming , Yuan Zhongying , Liu Jiani , Li Zhen , Sun Yanbin , Zhou Shanshan , Lu Gang , Huang Huicong , Zhao Wei
Published: July 2024

Wild rodents serve as reservoirs for Cryptosporidium and are overpopulated globally. However, genetic data regarding Cryptosporidium in these animals from China are limited. Here, we have determined the prevalence and genetic characteristics of Cryptosporidium among 370 wild rodents captured from three distinct locations in the southern region of Zhejiang Province, China. Fresh feces were collected from the rectum of each rodent, and DNA was extracted from them. The rodent species was identified by PCR amplifying the vertebrate cytochrome b gene. Cryptosporidium was detected by PCR amplification and amplicon sequencing the small subunit of ribosomal RNA gene. Positive samples of C. viatorum and C. parvum were further subtyped by analyzing the 60-kDa glycoprotein gene. A positive Cryptosporidium result was found in 7% (26/370) of samples, involving five rodent species: Apodemus agrarius (36), Niviventer niviventer (75), Rattus losea (18), R. norvegicus (155), and R. tanezumi (86). Their respective Cryptosporidium positive rates were 8.3%, 5.3%, 11.1%, 7.1%, and 7.0%. Sequence analysis confirmed the presence of three Cryptosporidium species: C. parvum (4), C. viatorum (1), and C. muris (1), and two genotypes: Cryptosporidium rat genotype IV (16) and C. mortiferum-like (4). Additionally, two subtypes of C. parvum (IIdA15G1 and IIpA19) and one subtype of C. viatorum (XVdA3) were detected. These results demonstrate that various wild rodent species in Zhejiang were concurrently infected with rodent-adapted and zoonotic species/genotypes of Cryptosporidium, indicating that these rodents can play a role in maintaining and dispersing this parasite into the environment and other hosts, including humans.
La Commission internationale d’optique le lieu de rencontre du monde de l’Optique
Authors: Westbrook Nathalie
Published: July 2024

Initiée au sortir de la 2e guerre mondiale pour rassembler une communauté de chercheurs en optique en Europe et aux Etats-Unis, la Commission Internationale d’Optique représente actuellement plus de 50 pays répartis sur les 5 continents. Elle fonctionne avec un bureau de 13 membres élus tous les 3 ans par les comités territoriaux des pays membres dont la SFO fait partie, et de 8 représentants d’autres sociétés savantes internationales, avec lesquelles elle mène de nombreuses actions. De nos jours, elle s’attache particulièrement à promouvoir l’Optique dans les pays en développement, notamment au travers de plusieurs prix qu’elle décerne et d’actions qu’elle soutient.
Optique frugale pour l’imagerie Infrarouge
Authors: Druart Guillaume , de la Barrière Florence , Gazzano Olivier , Fontbonne Alice
Published: July 2024

Le concepteur en optique est le plus souvent confronté à des critères conflictuels lorsqu’il s’agit de concevoir un système optique : performance versus taille, masse, consommation d’énergie et coût. Ceci l’amène à concevoir des optiques frugales.
Revising the role of belowground fungi in pentachlorophenol pollution management: insights from Tunisian cork oak forests
Authors: Varela Adélia , Pereira Cristina Silva
Published: July 2024

This summarizes the doctoral thesis “Belowground fungi are key sentinels in forest soils vulnerable to pentachlorophenol pollution: a mechanistic study in Quercus suber forests”. The PhD degree was awarded by ITQB NOVA in March 2018. It comprises a revision of the major issues, objectives, methodology and results, as well as a few possible recommendations for future work on bioremediation of halogenated aromatic pollutants. The working hypothesis of the thesis proposed that soils in Tunisian cork oak forests are likely contaminated with pentachlorophenol (PCP), a persistent organic pollutant (POP). This hypothesis is based on frequent reports of cork contamination with pentachloroanisole (PCA), which is likely formed through microbial conversion of PCP. Furthermore, PCP was considered a suitable model for investigating the role of soil mycobiota in pollution management due to its ability to travel long distances in the atmosphere, partition favourably into the soil layer, and moderate abiotic resistance, besides its life-threatening toxicity. Finally, fungi play a key role in colonizing soil in cork oak forests. These concepts have been applied in the "Preventive and remediation strategies for continuous elimination of polychlorinated phenols from forest soil" project (SfP-NATO 981674, 2006-2011). Overall the major findings of the study include the demonstration of the prevalence of PCP in the soils of Tunisian cork oak forests. Additionally, the study elucidated both the significance and impact of fungal activity in the mitigation and dispersion of PCP.
Grüne Nephrologie – was bedeutet dies für die Dialyseverfahren?
Authors: Boedecker-Lips Simone Cosima , Weinmann-Menke Julia
Published: July 2024

In Zeiten, in denen der Klimawandel durch die Erderwärmung immer deutlicher im Alltag der globalen Bevölkerung zu spüren ist, gilt: In allen Bereichen unseres menschlichen Handels (u.a. auch im Bereich der Medizin) ist ein Umdenken, hin zu einer umweltfreundlichen und klimaneutralen Lebensweise, unabdingbar. Im Bereich der Nephrologie ist daher zwingend eine Neuausrichtung der ressourcenintensiven Nierenersatztherapie nötig – Stichwort „Grüne Nephrologie“. Dabei muss zunächst das Bewusstsein für die verursachten CO2-Emissionen im Fachbereich Nephrologie geschärft werden, um dann in der Folge CO2-Einsparungen effizient umsetzen zu können. Dies wird zunächst unter Gebrauch der aktuell herkömmlichen Dialyseverfahren geschehen. Zudem werden zukünftig durch technische Weiterentwicklungen, wie portable und tragbare Hämo- und Peritonealdialyse-Geräte, deutliche Einsparungen an Energie- und Wasserverbrauch möglich sein. Des Weiteren führen innovative Forschungsansätze, wie Xenotransplantation, Stammzellforschung und der „künstliche“ Organersatz, zu neuen Alternativen zur Organtransplantation. Für die Nierenersatztherapie der Zukunft stehen somit unterschiedliche vielversprechende Ansätze zur Verfügung. Ziel der Nephrologie muss es nun sein, die Weiterentwicklung so voranzutreiben und zum Einsatz zu bringen, dass zeitnah eine umweltfreundliche Patient*innen-Versorgung in der Nephrologie möglich ist, um unseren Beitrag zum Klimaschutz zu leisten – bei gleichzeitiger Sicherstellung der Behandlung und ihrer Qualität.
Reciprocal interactions between neuropeptide F and RYamide regulate host attraction in the mosquito
Aedes aegypti
Authors: Dou Xiaoyi , Chen Kangkang , Brown Mark R. , Strand Michael R.
Published: July 2024

Female mosquitoes produce eggs in gonadotrophic cycles that are divided between a previtellogenic and vitellogenic phase. Previtellogenic females consume water and sugar sources like nectar while also being attracted to hosts for blood feeding. Consumption of a blood meal activates the vitellogenic phase, which produces mature eggs and suppresses host attraction. In this study, we tested the hypothesis that neuropeptide Y-like hormones differentially modulate host attraction behavior in the mosquito
Aedes aegypti
. A series of experiments collectively indicated that enteroendocrine cells (EECs) in the posterior midgut produce and release neuropeptide F (NPF) into the hemolymph during the previtellogenic phase which stimulates attraction to humans and biting behavior. Consumption of a blood meal, which primarily consists of protein by dry weight, down-regulated NPF in EECs until mature eggs developed, which was associated with a decline in hemolymph titer. NPF depletion depended on protein digestion but was not associated with EEC loss. Other experiments showed that neurons in the terminal ganglion extend axons to the posterior midgut and produce RYamide, which showed evidence of increased secretion into circulation after a blood meal. Injection of RYamide-1 and -2 into previtellogenic females suppressed host attraction, while coinjection of RYamides with or without short NPF-2 also inhibited the host attraction activity of NPF. Overall, our results identify NPF and RYamide as gut-associated hormones in
A. aegypti
that link host attraction behavior to shifts in diet during sequential gonadotrophic cycles.
Discharge mode and particle transport in radio frequency capacitively coupled Ar/O2 plasma discharges
Authors: Gao 高 Zhuo-Yao 卓瑶 , Dong 董 Wan 婉 , Tian 田 Chong-Biao 崇彪 , Jiang 蒋 Xing-Zhao 星照 , Dai 戴 Zhong-Ling 忠玲 , Song 宋 Yuan-Hong 远红
Published: July 2024

Simulations are conducted on capacitively coupled Ar/O2 mixed gas discharges employing a one-dimensional fluid coupled with an electron Monte Carlo (MC) model. The research explores the impact of different O2 ratio and pressures on the discharge characteristics of Ar/O2 plasma. At a fixed Ar/O2 gas ratio, with the increasing pressure, higher ion densities, as well as a slight increase in electron density in the bulk region can be observed. The discharge remains dominated by the drift–ambipolar (DA) mode, and the flux of O(3P) at the electrode increases with the increasing pressure due to higher background gas density, while the fluxes of O(1D) and Ar* decrease due to the pronounced loss rate. With the increasing proportion of O2, a change in the dominant discharge mode from α mode to DA mode can be detected, and the O2-associated charged particle densities are significantly increased. However, Ar+ density shows a trend of increasing and then decreasing, while for neutral fluxes at the electrode, Ar* flux decreases, and O(3P) flux increases with the reduced Ar gas proportion, while trends in O(1D) flux show slight differences. The evolution of the densities of the charged particle and the neutral fluxes under different discharge parameters are discussed in detail using the ionization characteristics as well as the transport properties. Hopefully, more comprehensive understanding of Ar/O2 discharge characteristics in this work will provide a valuable reference for the industry.
A combinatorial model for the moduli of bordered Riemann surfaces and a compactification
Authors: Kaufmann Ralph , Zúñiga Javier
Published: July 2024

We construct a combinatorial moduli space closely related to the KSV-compactification of the moduli space of bordered marked Riemann surfaces. The open part arises from symmetric metric ribbon graphs. The compactification is obtained by considering sequences of noncontractible subgraphs. This leads to a partial real blow-up of rational cells that together form a compact orbi-cell space. For genus zero the constructed space gives an orbi-cell decomposition of the corresponding analytic moduli space decorated by real numbers and a compactification of this space. In higher genus the relation is more involved, as we briefly explain. The spaces we construct are of interest in their own right as they are constructed directly from an interesting class of graphs.
Calculations for plus constructions
Authors: Monaco Michael
Published: July 2024

In recent work by Kaufmann and the author, we define a plus construction for monoidal categories and showed that if the monoidal category is a unique factorization category, then the plus construction yields a Feynman category. In this paper, we will use different methods to construct UFCs and demonstrate how the plus construction reproduces and clarifies existing constructions through explicit computations.
Segal conditions for generalized operads
Authors: Hackney Philip
Published: July 2024

This note is an introduction to several generalizations of the dendroidal sets of Moerdijk–Weiss. Dendroidal sets are presheaves on a category of rooted trees, and here we consider indexing categories whose objects are other kinds of graphs with loose ends. We examine the Segal condition for presheaves on these graph categories, which is one way to identify those presheaves that are a certain kind of generalized operad (for instance wheeled properad or modular operad). Several free/forgetful adjunctions between different kinds of generalized operads can be realized at the presheaf level using only the left Kan extension/restriction adjunction along a functor of graph categories. These considerations also have bearing on homotopy-coherent versions of generalized operads, and we include some questions along these lines.
Double covers of curves on Nikulin surfaces
Authors: D’Evangelista Simona , Lelli-Chiesa Margherita
Published: July 2024

We survey basic results concerning Prym varieties, the Prym-Brill-Noether theory initiated by Welters, and Brill-Noether theory of general étale double covers of curves of genus

g
≥
2

g\geq 2

. We then specialize to curves on Nikulin surfaces and show that étale double covers of curves on Nikulin surfaces of standard type do not satisfy Welters’ Theorem. On the other hand, by specialization to curves on Nikulin surfaces of non-standard type, we prove that general double covers of curves ramified at

b
=
2
,
4
,
6

b=2,4,6

points are Brill-Noether general; the case

b
=
2

b=2

was already obtained by Bud [The birational geometry of

R

g
,
2

¯

\overline {\mathcal {R}_{g,2}}

and Prym-canonical divisorial strata, math.AG/01718.v2] with different techniques.
O’Grady spaces and symplectic resolution of moduli spaces of Higgs bundles
Authors: Franco Emilio
Published: July 2024

We describe here a degeneration of the symplectic desingularization of the moduli spaces of topologically trivial

G
L

(
2
,

C

)

\mathrm {GL}(2,\mathbb {C})

and

S
L

(
2
,

C

)

\mathrm {SL}(2,\mathbb {C})

-Higgs bundles over a hyperelliptic curve, into O’Grady’s ten and six dimensional exceptional examples of irreducible holomorphic symplectic manifolds. Most of this note is a survey of work on these degenerations by Donagi–Ein–Lazarsfeld, de Cataldo–Maulik–Shen and Felisetti–Mauri, although in certain cases we provide details that were missing the previous articles.
Far-red light effects on plant photosynthesis: from short-term enhancements to long-term effects of artificial solar light
Authors: Lazzarin Martina , Dupont Killian , van Ieperen Wim , Marcelis Leo F M , Driever Steven M
Published: July 2024

Background and Aims

Long-term exposure over several days to far-red light (FR) increases leaf expansion, whereas short-term exposure (minutes) might enhance the photosystem II operating efficiency (ϕPSII). The interaction between these responses at different time scales and their impact on photosynthesis at the whole-plant level are not well understood. We aimed to assess the effects of FR in an irradiance mimicking the spectrum of sunlight (referred to as artificial solar irradiance), in both the long and short term, on whole-plant CO2 assimilation rates and in leaves at different positions in the plant.

Methods

Tomato (Solanum lycopersicum) plants were grown under artificial solar irradiance conditions with either a severely reduced or normal fraction of FR [SUN(FR−) vs. SUN]. To elucidate the interplay between the growth light treatment and the short-term reduction of FR, we investigated this interaction at both the whole-plant and leaf levels. At the whole-plant level, CO2 assimilation rates were assessed under artificial solar irradiance with a normal fraction and a reduced fraction of FR. At the leaf level, the effects of removal and presence of FR (0FR and 60FR) during transition from high to low light on CO2 assimilation rates and chlorophyll fluorescence were evaluated in upper and lower leaves.

Key Results

SUN(FR−) plants had lower leaf area, shorter stems and darker leaves than SUN plants. Although reducing FR during growth did not affect whole-plant photosynthesis under high light intensity, it had a negative impact at low light intensity. Short-term FR removal reduced both plant and leaf CO2 assimilation rates, but only at low light intensity and irrespective of the light treatment during growth and the leaf position. Interestingly, the kinetics of ϕPSII from high to low light were accelerated by 60FR, with a larger effect in lower leaves of SUN than in SUN(FR−) plants.

Conclusions

Growing plants with a reduced amount of FR light lowers whole-plant CO2 assimilation rates at low light intensity through reduced leaf area, despite maintaining similar leaf-level CO2 assimilation to leaves grown with a normal amount of FR. The short-term removal of FR brings about significant but marginal reductions in photosynthetic efficiency at the leaf level, regardless of the long-term growth light treatment.
Mental Health Rather than Mental Disorders as a Predictor of Immediate Postoperative Recovery After Elective Lumbar Fusion
Authors: Solomito Matthew J. , Kostyun Regina O. , Dzurec Laura , Makanji Heeren
Published: July 2024

Study Design.

Retrospective comparative cohort

Objective.

Investigate how a patient’s mental health, as measured using the PROMIS-10 Global Mental Health T score (MHT), influences their in-hospital recovery after elective 1- to 2-level lumbar fusion.

Summary of Background Data.

The intersection of mental and physical health among candidates for lumbar fusion has increased. Although there is strong evidence to suggest mental disorders can influence a patient’s postoperative recovery, there is a paucity of information detailing the association between unrecognized low mental health and surgical outcomes. The MHT may provide a more nuanced insight into a patient’s preoperative mental health status.

Methods.

A total of 637 patients who underwent 1- or 2-level elective lumbar fusion between April 2020 and June 2023 were analyzed for this study. Patients were stratified by their MHT (above average [AA] >50, control 40 to 50, below average [BA] <40) regardless of mental illness diagnosis. Outcome measures including pain scores both during activity and at rest, opioid consumption during the in-hospital stay, and ambulation distance were compared among groups using both univariate and multivariate models to control for confounders.

Results.

The majority of patients reported average (41.4%) to above-average (35.3%) mental health. After controlling for confounders, findings suggested that patients in the BA group reported higher pain, consumed more opioids, and had shorter ambulation distances than patients in the AA group (P=0.004, P=0.008, and P=0.020, respectively). Patients in the AA group were 84% less likely to be discharged to a facility than the BA group (P=0.001).

Conclusion.

The MHT was an independent predictor of immediate postsurgical recovery, whereas a mental disorder diagnosis was not. A preoperative MHT <40 may represent an additional risk factor that has not previously been identified in patients undergoing elective lumbar fusion.
Assessing the clinical outcomes of Dazhu Hongjingtian injection for the management of stable and unstable angina: Protocol for a prospective observational study
Authors: Song Tian , Che Qianzi , Liang Ning , Guo Jing , Liu Xiaoyu , Yang Lu , Jiang Yin , Shi Nannan , Wang Yanping
Published: July 2024

Background:

The global rise in angina pectoris, a symptom of coronary artery disease, is primarily attributed to an aging population and increasing prevalence of comorbidities. This study aims to assess the efficacy and safety of Dazhu Hongjingtian injection (DZHJTI) as an adjunct treatment for both stable and unstable angina, thereby addressing a significant gap in current cardiac care research.

Methods:

This comprehensive study involves 2 parallel prospective cohorts across 28 medical centers in China, enrolling 1500 patients with stable angina and 2000 with unstable angina. Participants are randomized into 2 groups: one receiving the DZHJTI alongside standard therapy and the other receiving standard therapy alone. The study employs advanced statistical methods like Subgroup Analysis and Marginal Mean Weighting Through Stratification to analyze data accurately.

Discussion:

The primary outcome of this study is the reduction in the frequency of angina attacks posttreatment. Secondary outcomes include the evaluation of patient well-being through clinical measures such as nitrate dosage requirements, vital sign stability, electrocardiogram changes, and laboratory data. Patient-reported outcomes from targeted questionnaires will also be assessed to understand the impact on quality of life. The study’s results are expected to contribute significantly to the understanding of DZHJTI’s role in treating angina pectoris, potentially influencing future treatment guidelines.
Identifying Genetic Mutations in Vascular Anomalies Using a Sequencing Panel for Childhood Cancers: A Pilot Study
Authors: Lee Elis Yuexian , Ang Yi Shan , Kuick Chik Hong , Mok Yingting , Chang Kenneth Tou En , Toh Luke Han Wei , Chan Mei Yoke , Koh Mark Jean Aan
Published: July 2024

Introduction:

Genetic mutations have been identified in the pathogenesis of vascular anomalies. Due to overlaps in genetic variants causing vascular anomalies and cancer, we used a next-generation sequencing panel for genomic profiling of childhood cancers to detect somatic mutations in children with vascular anomalies. We aim to review the utility of an oncology panel for the molecular diagnosis of vascular anomalies.

Methods:

Nine patients with histologically confirmed vascular anomalies were included. DNA was extracted from formalin-fixed paraffin-embedded tissue specimens obtained from affected tissue following diagnostic punch biopsies of the skin and core biopsies of the vascular malformation or tumor during sclerotherapy or surgical excision. Molecular analysis of the tissue samples was performed using AmpliSeq for Childhood Cancer DNA Assay Panel.

Results:

Two patients had antenatally detected vascular anomalies. The median age at diagnosis for the remaining patients was 7.0 years (IQR, 0.6–10.0 years). Seven were diagnosed with vascular malformations, while 2 had vascular tumors. Pathological somatic mutations were identified in 4 patients, leading to a diagnostic yield of 44.4%. Two different PIK3CA mutations were identified in 3 cases: 1 in a case of macrocystic lymphatic malformation, the other in a case of Congenital Lipomatous Overgrowth, Vascular malformations, Epidermal nevus, Spinal/Skeletal anomalies syndrome and Klippel–Trenaunay syndrome. BRAF mutation was identified in a patient with a veno-lymphatic malformation.

Conclusion:

An oncology next-generation sequencing panel can be used for genetic profiling of vascular anomalies. However, a more customized and sensitive panel may be of better diagnostic yield, as detection of somatic mutations in vascular anomalies is challenging due to tissue mosaicism, low-abundant genetic variants, and specimen limitations.
Role of vitamin D supplement adjunct to topical benzoyl peroxide in acne: a randomized double-blinded controlled study
Authors: Ruikchuchit Tin , Juntongjin Premjit
Published: July 2024

Background:

Acne is an inflammatory condition of the pilosebaceous unit. Previous studies have established a link between acne and vitamin D deficiency and the potential effectiveness of vitamin D supplementation in treatment. However, the efficacy of vitamin D as an adjuvant treatment for acne remains unknown.

Objective:

To evaluate the efficacy of weekly vitamin D2 oral administration as an adjunctive treatment to standard topical care for acne.

Methods:

This study was a randomized, double-blind, placebo-controlled trial including subjects with mild-to-moderate acne. Topical 2.5% benzoyl peroxide was applied twice daily for 12 weeks to all subjects. Subjects were randomly allocated to receive either oral vitamin D2 40,000 IU weekly or placebo weekly during the treatment period. No additional treatment was administered during the 4-week follow-up period.

Results:

A total of 44 subjects were included in this study. All of them had inadequate 25(OH)D levels. Both regimens showed significant improvement in acne during the treatment period. Weekly vitamin D2 supplementation significantly prevented the relapse of inflammatory acne lesions (P= .048) at the follow-up visit. No adverse effects or biochemical changes were observed.

Limitations:

There were no subjects of severe acne vulgaris.

Conclusion:

Adjunctive weekly vitamin D2 supplementation to standard topical benzoyl peroxide could reduce relapses of inflammatory lesions in mild-to-moderate acne.
Computed tomography angiography and coronary artery disease–reporting and data system and a 5-year prognostic major adverse cardiovascular and cerebral event outcome study in a symptomatic Southeast Asian population
Authors: Witoonchart Kan , Wannit Witoonchart , Kumpol Chintanavilas
Published: July 2024

Background

This study investigated the relationship between coronary artery disease–reporting and data system (CAD-RADS) for coronary computed tomography angiogram (CCTA) and major adverse cardiovascular and cerebral event (MACE) in a symptomatic Southeast Asian, Thai population over a 5-year period.

Methods

A retrospective cohort study of Thai patients without known CAD who underwent CCTA for CAD symptoms. CCTA images and 5-year health data were reviewed for CAD-RADS and MACE. MACE consists of all-cause mortality, cardiovascular death, acute coronary syndrome, heart failure hospitalization, and stroke.

Results

In total 336 patients were evaluated. The median follow-up period was 6.4 years. The overall MACE incidence was 63 cases (18.8%). The MACE event rate was progressively increased with higher CAD-RADS categories; CAD-RADS 3 [hazard ratio (HR), 3.62; P = 0.015], CAD-RADS 4a (HR, 3.50; P = 0.024), CAD-RADS 4b & 5 (HR, 7.56; P = 0.001). The risk of MACE increased significantly in the moderate to severe CAD burden group (HR, 5.58; P = 0.01). Kaplan–Meier curve showed a significant rise in MACE with higher CAD-RADS categories (P = 0.01).

Conclusion

CAD-RADS classification has a significant prognostic value in Southeast Asian, Thai population with cardiac symptoms.
Integrating the assessment of quality of life in care and research in pulmonary fibrosis
Authors: Aronson Kerri I. , Swigris Jeffrey J. , Wijsenbeek Marlies
Published: July 2024

Purpose of review

Pulmonary fibrosis (PF) negatively influences health-related quality of life (HRQOL). Patients living with PF have voiced the desire for a focus on symptoms and HRQOL in both disease monitoring and treatment decisions.

Recent findings

Currently available disease modifying treatments do little to impact HRQOL. Newer studies evaluating pharmacologic and nonpharmacologic therapies targeting symptoms and HRQOL in PF have been conducted with some promising results. There is increasing recognition of the importance of incorporating HRQOL as a higher tier endpoint in clinical trials. Disease-specific measure of HRQOL have been developed for those living with PF, and there is ongoing work to better understand the validity and reliability characteristics of these tools. In addition to research, there is recognition of the potential benefits of measuring HRQOL and symptoms in clinical practice in facilitate integrating patient perspective into care and allow for more personalized treatment approaches.

There is increased momentum to discover treatments that impact HRQOL in PF. More work is desperately needed to identify better treatment targets, and to incorporate HRQOL and symptoms as higher tier endpoints in clinical trials. Further work is also needed to address the practicalities of integrating HRQOL measurement into clinical care.
Sexual health in transgender and gender diverse people
Authors: Zhang Xinyuan , Neuville Paul , Skokan Alexander J.
Published: July 2024

Purpose of review

Sexual health and sexual function are critical to the wellbeing of cisgender, transgender, and gender diverse populations. To date, there has been only limited patient-focused evaluation of sexual function in transgender and gender diverse patients at several stages in their gender-affirming medical care. There remains a need to better understand the impact of gender affirming medical and surgical therapy on sexual health, and to develop evidence-based treatments to address sexual dysfunction when present.

Recent findings

The impact of gender-affirming hormone therapy on sexual health is complex and evolves over time on treatment. Despite high incidences of complications, major genital gender-affirming surgeries such as vulvovaginoplasty and penile implant placement after phalloplasty yield high patient satisfaction. While treatments to preserve or restore erections and to improve vaginal lubrication have been trialed based upon literature in cisgender populations, there remains minimal evidence to guide medical treatment of sexual dysfunction ranging from erectile dysfunction to dyspareunia.

There is a continued need for ongoing efforts to develop patient-reported outcome measures and rigorous investigation of sexual health preservation and restoration treatments in transgender and gender diverse populations.
Expanding the Spectrum of NUTM1-Rearranged Sarcoma
Authors: Zhu Peipei , Sun Ke , Lao I. Weng , Yu Lin , Bai Qianming , Zhou Xiaoyan , Wang Jian
Published: July 2024

Apart from the lethal midline carcinoma (NUT carcinoma), NUTM1 translocation has also been reported in mesenchymal tumors, but is exceedingly rare. Here, we describe a series of 8 NUTM1-rearranged sarcomas to further characterize the clinicopathologic features of this emerging entity. This cohort included 2 males and 6 females with age ranging from 24 to 64 years (mean: 51 y; median: 56 y). Tumors occurred in the colon (2), abdomen (2), jejunum (1), esophagus (1), lung (1) and infraorbital region (1). At diagnosis, 6 patients presented with metastatic disease. Tumor size ranged from 1 to 10.5 cm (mean: 6 cm; median: 5.5 cm). Histologically, 4 tumors were composed of primitive small round cells to epithelioid cells intermixed with variable spindle cells, while 3 tumors consisted exclusively of small round cells to epithelioid cells and 1 tumor consisted predominantly of high-grade spindle cells. The neoplastic cells were arranged in solid sheets, nests, or intersecting fascicles. Mitotic activity ranged from 1 to 15/10 HPF (median: 5/10 HPF). Other features included rhabdoid phenotype (4/8), pronounced nuclear convolutions (2/8), prominent stromal hyalinization (2/8), focally myxoid stroma (1/8), foci of osteoclasts (1/8), and necrosis (1/8). By immunohistochemistry, all tumors showed diffuse and strong nuclear staining of NUT protein, with variable expression of pancytokeratin (AE1/AE3) (2/8), CK18 (1/8), CD99 (3/8), NKX2.2 (2/8), cyclin D1 (2/8), desmin (2/8), BCOR (2/8), S100 (1/8), TLE1 (1/8), and synaptophysin (1/8). Seven of 8 tumors demonstrated NUTM1 rearrangement by fluorescence in situ hybridization analysis. RNA-sequencing analysis identified MXD4::NUTM1 (3/7), MXI1::NUTM1 (3/7), and MGA::NUTM1 (1/7) fusions, respectively. DNA-based methylation profiling performed in 2 cases revealed distinct methylation cluster differing from those of NUT carcinoma and undifferentiated small round cell and spindle cell sarcomas. At follow-up (range: 4 to 24 mo), 1 patient experienced recurrence at 8.5 months, 4 patients were alive with metastatic disease (5, 10, 11, and 24 mo after diagnosis), 3 patients remained well with no signs of recurrence or metastasis (4, 6, and 12 mo after diagnosis). Our study further demonstrated that NUTM1-rearranged sarcoma had a broad range of clinicopathologic spectrum. NUT immunohistochemistry should be included in the diagnostic approach of monotonous undifferentiated small round, epithelioid to high-grade spindle cell malignancies that difficult to classify by conventional means. DNA-based methylation profiling might provide a promising tool in the epigenetic classification of undifferentiated sarcomas.
Methods of diagnostic meta-analysis: comparing the generalized linear mixed model and the split component synthesis model
Authors: Zar Lubna A. , Alsharif Fatima R. , Zar Amna , Alwisi Nouran , Tluli Omar , Syed Asma , Doi Suhail A.
Published: July 2024

Purpose of review

Diagnostic meta-analyses combine data from several diagnostic test accuracy (DTA) studies to provide an in-depth assessment of a specific diagnostic test's performance across diverse populations and settings. Additionally, knowledge on common methods of diagnostic meta-analyses is crucial for researchers to make informed decisions on best practice for reporting analyses and results. This article provides an overview of commonly used methods of diagnostic meta-analyses using real-life and simulation data.

Recent findings

Advances in methods of diagnostic meta-analyses in recent years have increased uncertainty among researchers in relation to the most suitable method to be used. Currently, the most popular approaches for diagnostic evidence synthesis include hierarchical summary operating characteristic (HSROC) and bivariate random effects models though other methods such as the split component synthesis method have been proposed. In addition, different software modules exist for DTA meta-analyses.

This article presents a thorough evaluation of current frequentist DTA meta-analysis methods implementing both simulated and real-world data. By understanding the recent methods of diagnostic meta-analyses and their limitations, clinicians may better be equipped in selecting the optimum approach to improve clinical judgement and consequently better patient outcomes.
Describing and assessing behavioural symptoms in amyotrophic lateral sclerosis with and without frontotemporal dementia: a scoping review
Authors: Trucco Ana Paula , Backhouse Tamara , Mioshi Eneida
Published: July 2024

Purpose of review

Alongside motor and cognitive symptoms, amyotrophic lateral sclerosis (ALS) and ALS with frontotemporal dementia (ALSFTD) present with behavioural symptoms, which can be challenging for all affected by the disease. A scoping review of studies published between 2011 and 2024 was conducted to present the breadth of behavioural symptoms in ALS and ALSFTD, explore how they are described and assessed, and identify patterns in the literature.

Findings

This scoping review identified 3939 articles, with 111/3939 meeting eligibility criteria. Most studies were from Australia (23.22%), Italy (16.94%) and the UK (14.29%); 75.67% were cross-sectional. Sample size ranged from 1 to 1013, as case studies were included. Overall mean age (100/111 studies) was 61.32 (SD = 4.15). Proportion of male patients (reported 102/111 studies) was 61.49%; mean disease duration (reported in 86/111 records) was 32.63 months (SD = 24.72). Papers described a broad range of behavioural symptoms (465 examples), which were thematically collated into seven categories: disinhibition (27.74%), apathy (25.16%), perseverative/compulsive behaviours (17.42%), hyperorality (10.53%), loss of sympathy or empathy (8.6%), psychotic symptoms (7.74%), and loss of insight about disease and changes (2.8%). Most studies (78.37%) used validated behavioural assessments that elicited carer's perspectives.

Despite extensive evidence of behavioural symptoms in ALS, implementation of assessments and management of behavioural symptoms in clinical care remain limited. Clinicians must assess behavioural symptoms, as these can negatively affect disease prognosis, patient treatment engagement and increase family distress. Measures capturing carers’ perspectives through interviews are ideal as they can reveal anosognosia, lack of sympathy and lack of empathy.
Unlocking a New Path: An Autophagometer that Measures Flux Using a Non-Fluorescent Immunohistochemistry Method
Authors: Shojaei Shahla , Barzegar Behrooz Amir , Cordani Marco , Aghaei Mahmood , Azarpira Negar , Klionsky Daniel J. , Ghavami Saeid
Published: July 2024

Macroautophagy/autophagy, a crucial cellular process, is typically measured using fluorescence-based techniques, which can be costly, complex, and impractical for clinical settings. In this paper, we introduce a novel, cost-effective, non-fluorescent immunohistochemistry (IHC) method for evaluating autophagy flux. This technique, based on antigen-antibody reactions and chromogenic detection, provides clear, quantifiable results under standard light microscopy, eliminating the need for expensive equipment and specialized reagents. Our method simplifies technical requirements, making it accessible to routine clinical laboratories and research settings with limited resources. By comparing our approach with traditional fluorescence methods, we demonstrate its superior effectiveness, cost-efficiency, and applicability to patient samples. This innovative technique has the potential to significantly advance autophagy research and improve clinical diagnostics, offering a practical and robust tool for studying autophagy mechanisms in diseases such as cancer and neurodegenerative disorders. Our non-fluorescent IHC method represents a significant step forward in evaluating autophagy flux, making it more accessible and reliable, with the promise of enhancing our understanding and treatment of autophagy-related diseases.
Dopamine transmission at D1 and D2 receptors in the nucleus accumbens contributes to the expression of incubation of cocaine craving
Authors: Weber Sophia J. , Kawa Alex B. , Moutier Alana L. , Beutler Madelyn M. , Koyshman Lara M. , Moreno Cloe D. , Westlake Jonathan G. , Wunsch Amanda M. , Wolf Marina E.
Published: July 2024

Relapse represents a consistent clinical problem for individuals with substance use disorder. In the incubation of craving model of persistent craving and relapse, cue-induced drug seeking progressively intensifies or ‘incubates’ during the first weeks of abstinence from drug self-administration and then remains high for months. Previously, we and others have demonstrated that expression of incubated cocaine craving requires strengthening of excitatory synaptic transmission in the nucleus accumbens core (NAcc). However, despite the importance of dopaminergic signaling in the NAcc for motivated behavior, little is known about the role that dopamine (DA) plays in the incubation of cocaine craving. Here we used fiber photometry to measure DA transients in the NAcc of male and female rats during cue-induced seeking tests conducted in early abstinence from cocaine self-administration, prior to incubation, and late abstinence, after incubation of craving has plateaued. We observed DA transients time-locked to cue-induced responding but their magnitude did not differ significantly when measured during early versus late abstinence seeking tests. Next, we tested for a functional role of these DA transients by injecting DA receptor antagonists into the NAcc just before the cue-induced seeking test. Blockade of either D1 or D2 DA receptors reduced cue-induced cocaine seeking after but not before incubation. We found no main effect of sex in our experiments. These results suggest that DA contributes to incubated cocaine seeking but the emergence of this role reflects changes in postsynaptic responsiveness to DA rather than presynaptic alterations.
Epigenetic memory of temperature sensed during somatic embryo maturation in 2-year-old maritime pine trees
Authors: Trontin J.-F. , Sow M.D. , Delaunay A. , Modesto I. , Teyssier C. , Reymond I. , Canlet F. , Boizot N. , Le Metté C. , Gibert A. , Chaparro C. , Daviaud C. , Tost J. , Miguel C. , Lelu-Walter M.-A. , Maury S.
Published: July 2024

Embryogenesis is a brief but potentially critical phase in the tree life cycle for adaptive phenotypic plasticity. Using somatic embryogenesis in maritime pine, we found that temperature during the maturation phase affects embryo development and post-embryonic tree growth for up to three years. We examined whether this somatic stress memory could stem from temperature- and/or development-induced changes in DNA methylation. To do this, we developed a 200 Mb custom sequence capture bisulfite analysis of genes and promoters to identify differentially methylated cytosines (DMCs) between temperature treatments (18, 23, and 28°C) and developmental stages (immature and cotyledonary embryos, shoot apical meristem of 2-year-old plants) and investigate if these differences can be mitotically transmitted from embryonic to post-embryonic development (epigenetic memory). We revealed a high prevalence of temperature-induced DMCs in genes (8-14%) compared to promoters (less than 1%) in all 3 cytosine contexts. Developmental DMCs showed a comparable pattern but only in the CG context, and with a high trend towards hypo-methylation, particularly in the promoters. A high percentage of DMCs induced by developmental transitions were found memorized in genes (up to 45-50%) and promoters (up to 90%). In contrast, temperature-induced memory was lower and confined to genes after both embryonic (up to 14%) and post-embryonic development (up to 8%). Using stringent criteria, we identified ten genes involved in defense responses and adaptation, embryo development and chromatin regulation that are candidates for the establishment of a persistent epigenetic memory of temperature sensed during embryo maturation in maritime pine.

Graphical abstract
Reversible control of kinase signaling through chemical-induced dephosphorylation
Authors: Sun Ying , Zhou Rihong , Hu Jin , Feng Shan , Hu Qi
Published: July 2024

The coordination between kinases and phosphatases is crucial for regulating the phosphorylation levels of essential signaling molecules. Methods enabling precise control of kinase activities are valuable for understanding the kinase functions and for developing targeted therapies. Here, we use the abscisic acid (ABA)-induced proximity system to reversibly control kinase signaling by recruiting phosphatases. Using this method, we found that the oncogenic tyrosine kinase BCR::ABL1 can be inhibited by recruiting various cytoplasmic phosphatases. We also discovered that the oncogenic serine/threonine kinase BRAF(V600E), which has been reported to bypass phosphorylation regulation, can be positively regulated by protein phosphatase 1 (PP1) and negatively regulated by PP5. Additionally, we observed that the dual-specificity kinase MEK1 can be inhibited by recruiting PP5. This suggests that bifunctional molecules capable of recruiting PP5 to MEK or RAF kinases could be promising anticancer drug candidates. Thus, the ABA-induced dephosphorylation method enables rapid screening of phosphatases to precisely control kinase signaling.
Colony context and size-dependent compensation mechanisms give rise to variations in nuclear growth trajectories
Authors: Dixon Julie C. , Frick Christopher L. , Leveille Chantelle L. , Garrison Philip , Lee Peyton A. , Mogre Saurabh S. , Morris Benjamin , Nivedita Nivedita , Vasan Ritvik , Chen Jianxu , Fraser Cameron L. , Gamlin Clare R. , Harris Leigh K. , Hendershott Melissa C. , Johnson Graham T. , Klein Kyle N. , Oluoch Sandra A. , Thirstrup Derek J. , Sluzewski M. Filip , Wilhelm Lyndsay , Yang Ruian , Toloudis Daniel M. , Viana Matheus P. , Theriot Julie A. , Rafelski Susanne M.
Published: July 2024

To investigate the fundamental question of how cellular variations arise across spatiotemporal scales in a population of identical healthy cells, we focused on nuclear growth in hiPS cell colonies as a model system. We generated a 3D timelapse dataset of thousands of nuclei over multiple days, and developed open-source tools for image and data analysis and an interactive timelapse viewer for exploring quantitative features of nuclear size and shape. We performed a data-driven analysis of nuclear growth variations across timescales. We found that individual nuclear volume growth trajectories arise from short timescale variations attributable to their spatiotemporal context within the colony. We identified a strikingly time-invariant volume compensation relationship between nuclear growth duration and starting volume across the population. Notably, we discovered that inheritance plays a crucial role in determining these two key nuclear growth features while other growth features are determined by their spatiotemporal context and are not inherited.
A distinct isoform of Msp300 (nesprin) organizes the perinuclear microtubule organizing center in adipocytes
Authors: Morton Garret M. , Toledo Maria Pilar , Zheng Chunfeng , Zheng Yiming , Megraw Timothy L.
Published: July 2024

In many cell types, disparate non-centrosomal microtubule-organizing centers (ncMTOCs) replace functional centrosomes and serve the unique needs of the cell types in which they are formed. In Drosophila fat body cells (adipocytes), an ncMTOC is organized on the nuclear surface. This perinuclear ncMTOC is anchored by Msp300, encoded by one of two nesprin-encoding genes in Drosophila. Msp300 and the spectraplakin short stop (shot) are co-dependent for localization to the nuclear envelope to generate the ncMTOC where they recruit the microtubule minus-end stabilizer Patronin (CAMSAP). TheMsp300gene is complex, encoding at least eleven isoforms. Here we show that two Msp300 isoforms, Msp300-PE and -PG, are required and only one, Msp300-PE, appears sufficient for generation of the ncMTOC. Loss of Msp300-PE and -PG results in severe loss of localization of shot and Patronin, disruption of the MT array, nuclear mispositioning and loss of endosomal trafficking. Furthermore, upon loss of Msp300-PE and -PG, other isoforms are retained at the nuclear surface despite the loss of nuclear positioning and MT organization, indicating that they are not sufficient to generate the ncMTOC. Msp300-PE has an unusual domain structure including a lack of a KASH domain and very few spectrin repeats and appears therefore to have a highly derived function to generate an ncMTOC on the nuclear surface.