bluuebunny/crossref_metadata_2025 huggingface dataset:
(078) VASAL FLUID MICROSCOPIC APPEARANCE AND GRADE AS A PROGNOSTIC MARKER FOR PATENCY IN REDO-VASECTOMY REVERSALS: A RETROSPECTIVE REVIEW OF SURGICAL OUTCOMES
Authors: Mubarak M , Mukherjee A , Jesuraj N , Shaw W , Jesuraj M
Published: December 2024

Introduction

Due to a myriad of reasons, vasectomy reversal (VR) is requested by up to 6% of men who have previously had a vasectomy. Current surgical and technical advances in VR have led to high patency and pregnancy rates. However, there remains a subset of patients who desire natural conception but fail VR. Redo-VR is a feasible option to achieve paternity for this specific subset of patients.

Objective

This study aims to evaluate our own experience with redo-VR patients and factors contributing to a successful outcome in the form of patency rates.

Methods

This is a retrospective review of a prospectively updated patient database. Patients who had a redo vasectomy reversal with either a vasovasotomy (VV) or a vaso-epididymostomy (VE) were included in the review. Outcomes of interest included patient age, partner age, obstructive interval (OI), intra-operative vasal fluid microscopy findings and post-operative patency rates. The Silber 1977 grading system was used to describe vasal fluid microscopic findings. Data was extracted and organised using Microsoft Excel, and further analysis was done using SPSS v29. A p-value of <0.05 was considered significant.

Results

Seventy two (72) patients were eligible for review and had complete records. The average age was 48.8 +/- 7.6 years, with an average partner age of 32.9 +/-4.2 years. The average number of years since the initial vasectomy or OI was 10 years. The majority (63.8%) had bilateral vasovasostomy. Vasal microscopic fluid appearances are described in the figure with less than half having Silber Scale 1. The overall patency rate of the redo-reversal procedures was 82%. A Cochrane-Armitage test demonstrated that Silber classification of vasal fluid on microscopy did not predict successful outcomes (p = 0.66). Patients with redo-VE had lower patency rates.

Conclusions

Redo-VR is a feasible option for patients seeking natural conception after a vasectomy and an unsuccessful reversal procedure. Our findings demonstrate post-operative patency rates similar to primary VR patency rates described in the literature. Silber scale does not reliably predict outcomes.

Disclosure

No.
(085) OPTIMAL RESTORATION OF SPERMATOGENESIS FOLLOWING TESTOSTERONE THERAPY USING HCG AND FSH
Authors: Stocks B , Oppenheimer A , Huang J , Lipshultz L
Published: December 2024

Introduction

Testosterone monotherapy impedes spermatogenesis and often renders the male user azo- or severely oligospermic. Prior studies have demonstrated that rescue Human Chorionic Gonadotropin (HCG) and Clomiphene Citrate therapy can restore semen parameters, but report that just under half of men will respond favorably.

Objective

In the present study, we hypothesized that direct gonadotropic stimulation with HCG and purified Follicle Stimulating Hormone (FSH) (in lieu of indirect clomiphene-mediated FSH release) would result in improved recovery of spermatogenesis in oligospermic men with a history of testosterone use. Secondarily, we questioned whether concomitant use of Testosterone therapy during HCG/FSH “rebooting” of the testicles would dampen spermatogenic recovery as compared to those ceasing Testosterone therapy.

Methods

We performed a retrospective cohort study and identified 288 patients prescribed injections of 3000 IU HCG three times a week (TIW) and 75 IU FSH TIW from January 2020-March 2024 (we termed this therapy “reboot”). We then excluded those patients without prior use of testosterone replacement therapy (TRT), those with only one documented semen analysis, and those starting with normospermia (>15 million [M] sperm per mL). Our final cohort included 77 patients meeting these strict criteria, 50 of whom were not on concurrent testosterone replacement therapy during reboot (No TRT), and 27 of whom were (Concurrent TRT). Patient demographics, testicular size, hormone levels, and semen analyses during treatment were then compared between groups. Student’s t-test and One or Two-way ANOVA with multiple comparisons were used. P < 0.05 deemed significance.

Results

Within our cohort, 74% of all treated patients demonstrated an improvement in their semen parameters (mean duration of treatment 7 months); mean sperm concentrations increased from 2.2 M/mL to 15.2 M/mL after reboot (p < 0.0001 by paired t-test). Of those patients starting with azoospermia, 64.9% demonstrated return of sperm and 13.5% reached normospermia. Of those starting with severe oligospermia (<5 M/mL), 58.3% reached normospermia, and of those starting with oligospermia (>5 but <15 M/mL) 87.5% reached normospermia. Concurrent TRT during HCG/FSH reboot did not dampen spermatogenic recovery: 2.2 M/mL to 16.8 M/mL in the No TRT group and 2.2 M/mL to 12.3 M/mL in the Concurrent TRT group (p < 0.0001 by paired t-test).

Conclusions

We report the largest retrospective cohort study to date investigating the utility of gonadotropic HCG/FSH “reboot” therapy in restoring spermatogenesis in men with a history of testosterone use. Setting the groundwork for future prospective studies, we report improved recovery of spermatogenesis with this therapeutic regimen vs. conventional HCG/clomiphene citrate therapy. Moreover, we demonstrate that concurrent TRT does not impede HCG/FSH mediated spermatogenic recovery.

Disclosure

No.
British Perceptions of Cyprus and the Production of Ceramics from 1809 to 1920
Authors: Reeve Anna
Published: December 2024

The advent of British administration of Cyprus in 1878 brought this Mediterranean island to the attention of the British public, whose perceptions and beliefs formed an important context for the development of Government policy. This article draws on representations of Cyprus in British-made ceramics from 1809 to 1920, to explore what the idea of Cyprus conveyed to their manufacturers and consumers both before and after the events of 1878. It also considers the impact of the arrival of ancient Cypriot pottery on the British auction market and in museums from around 1870, especially the efforts made in South Kensington and Staffordshire to provide access to Cypriot ceramics as models for design. It investigates how artists and designers drew on these antiquities in creating their own work, leading to their circulation in new forms beyond antiquarian networks. It examines a range of ceramic productions, from mass-produced transferware and souvenir ornaments to art pottery, analysing their forms and decoration, and exploring how these relate to their social and cultural contexts. Material culture, such as ceramics, offers a fresh way of exploring changes in perceptions and attitudes towards Cyprus over time.
The influence of the cloud virial parameter on the initial mass function
Authors: Mathew Sajay Sunny , Federrath Christoph , Seta Amit
Published: December 2024

Crucial for star formation is the interplay between gravity and turbulence. The observed cloud virial parameter, $\alpha _{\mathrm{vir}}$, which is the ratio of twice the turbulent kinetic energy to the gravitational energy, is found to vary significantly in different environments, where the scatter among individual star-forming clouds can exceed an order of magnitude. Therefore, a strong dependence of the initial mass function (IMF) on $\alpha _{\mathrm{vir}}$ may challenge the notion of a universal IMF. To determine the role of $\alpha _{\mathrm{vir}}$ on the IMF, we compare the star-particle mass functions obtained in high-resolution magnetohydrodynamical simulations including jet and heating feedback, with $\alpha _{\mathrm{vir}}=0.0625$, 0.125, and 0.5. We find that varying $\alpha _{\mathrm{vir}}$ from $\alpha _{\mathrm{vir}}\sim 0.5$ to $\alpha _{\mathrm{vir}}< 0.1$ shifts the peak of the IMF to lower masses by a factor of $\sim 2$ and increases the star formation rate by a similar factor. The dependence of the IMF and star formation rate on $\alpha _{\mathrm{vir}}$ is non-linear, with the dependence subsiding at $\alpha _{\mathrm{vir}}< 0.1$. Our study shows a systematic dependence of the IMF on $\alpha _{\mathrm{vir}}$. Yet, it may not be measurable easily in observations, considering the uncertainties, and the relatively weak dependence found in this study.
DNA binding and transposition activity of the Sleeping Beauty transposase: role of structural stability of the primary DNA-binding domain
Authors: Ranjan Venkatesh V , Leighton Gage O , Yan Chenbo , Arango Maria , Lustig Janna , Corona Rosario I , Guo Jun-Tao , Nesmelov Yuri E , Ivics Zoltán , Nesmelova Irina V
Published: December 2024

DNA transposons have emerged as promising tools in both gene therapy and functional genomics. In particular, the Sleeping Beauty (SB) DNA transposon has advanced into clinical trials due to its ability to stably integrate DNA sequences of choice into eukaryotic genomes. The efficiency of the DNA transposon system depends on the interaction between the transposon DNA and the transposase enzyme that facilitates gene transfer. In this study, we assess the DNA-binding capabilities of variants of the SB transposase and demonstrate that the structural stability of the primary DNA-recognition subdomain, PAI, affects SB DNA-binding affinity and transposition activity. This fundamental understanding of the structure–function relationship of the SB transposase will assist the design of improved transposases for gene therapy applications.
DNA metabarcoding reveals dietary divergence among sympatric swallows and flycatchers
Authors: Nancekivell Pat R , Nocera Joseph J
Published: December 2024

Aerial insectivore (AI) populations have been in steep decline in North America since the 1970s, with swallows, swifts, and nightjars declining more rapidly than flycatchers. As AIs share a common diet of flying insects, reductions in insect abundance are likely one of the major factors driving population decline. Previous studies have shown major dietary differences between swallows and flycatchers; flycatchers have exhibited more diverse, generalist diets than swallows. However, no study has directly compared the diets of sympatric swallows and flycatchers using the same method of dietary analysis. To investigate these differences, we compared the diets of 6 AI species living in sympatry during the breeding season. We collected fecal samples from adult Riparia riparia (Bank Swallow), Hirundo rustica (Barn Swallow), Petrochelidon pyrrhonota (Cliff Swallow), Tachycineta bicolor (Tree Swallow), Empidonax alnorum (Alder Flycatcher), and E. minimus (Least Flycatcher). We used DNA metabarcoding to identify the taxonomic composition of invertebrates in the feces and compared the richness of genera by insect order, insect family, and dipteran family between all species. Through a Bray-Curtis distance-based redundancy analysis, we identified significant differences in dietary composition between bird species at all 3 levels; however, the greatest amount of dissimilarity is seen in the dipterans consumed. Empidonax alnorum, E. minimus, H. rustica, and T. bicolor had broader, more generalist diets than P. pyrrhonota and R. riparia. By comparing the diets of multiple species living in sympatry, our study improves our understanding of a possible cause of disproportionate population declines observed among AI species.
Haemosporidian infection does not alter aerobic performance in Junco hyemalis (Dark-eyed Junco)
Authors: Stager Maria , Eddy Douglas K , Elowe Cory R , Cheviron Zachary A , Carling Matthew D
Published: December 2024

Avian haemosporidia are blood parasites that can have dramatic fitness consequences on their hosts, including largescale population declines when introduced to naïve hosts. Yet the physiological effects that accompany haemosporidian infection and underlie these fitness decrements are poorly characterized in most wild birds. Because haemosporidia destroy host red blood cells and consume host hemoglobin, they are predicted to have detrimental impacts on avian blood-oxygen transport and, as a result, reduce aerobic performance. However, the documented effects of infection on avian hematological traits vary across species and no effects have been demonstrated on avian aerobic performance to date. Here we quantified the physiological effects of haemosporidian infections on wild Junco hyemalis (Dark-eyed Junco) breeding in northwestern Wyoming, USA. We assayed hematological traits (hemoglobin concentration and hematocrit) and aerobic performance (resting and summit metabolic rates, thermogenic endurance, and aerobic scope), then screened individuals for haemosporidian infection by quantitative PCR post-hoc (n = 110 adult juncos). We found that infection status and infection intensity did not significantly correlate with any of the physiological indices that we measured, suggesting there is little cost of haemosporidian infection on either junco aerobic performance or energy budgets. The fact that our results contradict predicted outcomes highlights the need for more studies of haemosporidia infections in a broader range of species and in a wider array of environmental contexts.
Hegemonic defeatism: The mainstreaming of far-right politics in France
Authors: Mondon Aurelien
Published: December 2024

Another European election, another ‘earthquake’ in France. For the third time in a row, the far-right Rassemblement National has won and for the third time, the reaction from the mainstream elite only serves to further mainstream its politics. This could not be better exemplified than in Emmanuel Macron’s decision to call for a new legislative election and appoint a right-wing Prime Minister, despite the results. The aim of this article is to couch the French case in a different light to that which is usually applied to understanding the rise of the far right. To understand what is happening in France and the crisis it (and other democracies) is facing, we must take a longer-view approach. Instead of focussing on the far right itself, this article examines the past 50 years through a lens that focuses on power and those in a particularly privileged position to shape the agenda and public discourse. This demonstrates how a different, more critical approach to the rise of the far right, which accounts for the central role of mainstream elites, can help us not only better understand this rise, but offer alternatives beyond the current hegemonic defeatism.
Evidence for decoupled water potential between myco- and photobionts during desiccation in the tripartite lichen Peltigera britannica
Authors: Petruzzellis Francesco , Boccato Enrico , Musso Carlotta , Craighero Teresa , Montagner Alice , Savi Tadeja , Muggia Lucia , Tønsberg Tor , Tretiach Mauro , Nardini Andrea , Candotto Carniel Fabio
Published: December 2024

In lichens, accurate description of thallus water status is required to understand growth and photosynthesis dynamics. A recent model suggested that myco- and photobiont layers could have a different water energy status (i.e. a different water potential, Ψ) during thallus desiccation, but data supporting this hypothesis were presented only for one chlorolichen. We compared water relations and maximum photosystem II (PSII) efficiency during desiccation in the tripartite lichen Peltigera britannica and its axenically cultured photobionts, the green alga Coccomyxa sp. and the cyanobacterium Nostoc sp. To assess whether myco- and photobiont layers had different Ψ values during desiccation, we expected that (i) water relation parameters differ between cultured photobionts and entire thalli and (ii) Ψ values inducing a significant drop in PSII efficiency are lower for entire thalli than for cultured photobionts. We found that photobionts had very different water relation parameters than entire thalli, i.e. lower water potential at the turgor loss point and higher cell wall elasticity, irrespective of the photobiont type, potentially underlying a different drought tolerance. PSII efficiency in entire thalli and cultured photobionts started to decrease below Ψ values, inducing turgor loss. Importantly, PSII efficiency in entire thalli decreased at Ψ values significantly more negative than those inducing turgor loss in cultured photobionts. These data support the hypothesis of decoupled Ψ between myco- and photobionts in lichens during desiccation. A higher Ψ ensured to the photobiont layer might represent a key adaptation to prolong photosynthesis during desiccation.
Similarities and differences in self-reported symptoms and comorbidities between hypermobile Ehlers–Danlos syndrome and hypermobility spectrum disorders
Authors: Darakjian Ashley A , Bhutani Mira , Fairweather DeLisa , Kocsis S Christian , Fliess Jessica J , Khatib Sami , Weigel Gabe J , McCabe Elizabeth J , Balamurugan Varsini , Perona Evan E , Gehin Jessica M , Whelan Emily R , Jain Angita , Sledge Hanna , Hodge David O , Rozen Todd D , Farraye Francis A , Soyer Ozan , Cheung Joseph , Grach Stephanie L , Shirey Jr. David , Gajarawala Shilpa , Munipalli Bala , Shufelt Chrisandra L , Knight Dacre R T , Bruno Katelyn A
Published: December 2024

Objectives

Patients with hypermobile Ehlers–Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD) experience a wide array of symptoms and system disorders. This study aimed to identify whether differences occurred in 115 self-reported symptoms and comorbidities in patients diagnosed with hEDS or HSD.

Methods

In this study we analysed self-reported data from an EDS Clinic intake questionnaire in patients diagnosed with hEDS, HSD or no hypermobile conditions.

Results

From 1 November 2019 to 7 March 2024, the EDS Clinic saw 2088 patients. Using the 2017 diagnostic criteria, 66.5% were diagnosed with HSD (n = 1389), 20.3% with hEDS (n = 423), 10.6% with historic HSD (H-HSD) or localized HSD (L-HSD) (n = 256) (hypermobile controls) and 2.6% were not diagnosed with hEDS, HSD, H-HSD or L-HSD (n = 55) (controls). Symptoms/comorbidities that occurred with high prevalence in both hEDS and HSD included joint pain (hEDS 82.0%, HSD 88.9%), allergy (hEDS 77.0%, HSD 77.0%), subluxations (hEDS 71.2%, HSD 72.6%), brain fog (hEDS 70.0%, HSD 74.7%), headache (hEDS 68.1%, HSD 69.1%), anxiety (hEDS 60.3%, HSD 69.3%), depression (hEDS 52.2%, HSD 58.0%), migraine (hEDS 53.7%, HSD 52.5%), nausea (hEDS 54.6%, HSD 59.5%) and constipation (hEDS 53.0%, HSD 57.2%). In contrast, 9/115 (8%) symptoms/comorbidities were self-reported significantly more often in hEDS but 42/115 (37%) in HSD. hEDS patients reported more symptoms that suggest a defect in collagen, such as dislocation, hernias and rectal prolapse, while HSD patients reported more joint, muscle, allergy, neurological, gastrointestinal, sleep and psychological symptoms/comorbidities.

Conclusion

Although we found an overlap in some symptoms and comorbidities self-reported by hEDS/HSD patients, such as allergy/atopy, headache/migraine and gastrointestinal symptoms, our findings suggest key differences exist between the two diagnoses, suggesting that hEDS and HSD may be distinct conditions.
The decoupling of socioeconomic status, postmaterialism, and environmental concern in an unequal world: a cross-national intercohort analysis
Authors: Wang Yan
Published: December 2024

There has been an intense yet inconclusive debate over the impacts of socioeconomic status (SES) and postmaterialism on environmental concern. Recent years have seen a growing interest in addressing the controversy by exploring the conditioning effect of social context. Previous studies of inequality argue that it unevenly exposes people to environmental degradation, reduces social cooperation, and erodes egalitarian values. This study integrates the two lines of research by linking social inequality to environmental sustainability and examines the extent to which inequality shapes the impact of SES and postmaterialism on environmental concern in the cross-national intercohort context. Analyses of multiple waves of the World Values Survey data using the hierarchical age-period-cohort modeling techniques suggest that contextual inequality substantially attenuates the effects of SES and postmaterialism. This relationship is consistent across countries with different economic development levels and more pronounced in older cohorts. The current study illustrates the importance of careful consideration of social conditions, the unequal distribution of income in particular, when examining predictors of environmental concern, and sheds light on the theorization of a more inclusive, balanced human-nature relationship.
The COVID-19 crisis as a double-edged revealer: Japanese employees’ hope for change in corporate warrior culture and the gendered impediments to such change
Authors: Goldstein-Gidoni Ofra
Published: December 2024

In Japan, the COVID-19 pandemic unfolded amidst a heated debate about the country’s ‘working style’, work–life balance (or lack thereof), and a growing recognition of the urgent need for comprehensive change in the prevailing work culture. This article proposes that the crisis acted as a double-edged ‘revealer’. As such, it simultaneously raised employees' hopes that the crisis would trigger change in the masculine corporate warrior culture, while exposing the deeply entrenched impediments to this desired change. Beginning with the public debate about the crisis as a potential trigger for change in the so-called ‘Japanese’ work culture, which has also fuelled hopes for change, the article examines the narratives of employees forced into new forms of flexible working by the COVID-19 pandemic. These female and male accounts shed light on gendered experiences of work, and perceptions of what constitutes the ‘Japanese’ ideal worker. The accounts also reveal a growing and troubling awareness of the barriers to change in the culture of work.
The chondrogenic potential of the bovine tendon sheath—a novel source of stem cells for cartilage repair
Authors: Hunziker Ernst B , Nishii Naomi , Shintani Nahoko , Lippuner Kurt , Keel Marius J B , Voegelin Esther
Published: December 2024

The human hand is traumatized more frequently than any other bodily part. Trauma and pathological processes (eg, rheumatoid arthritis, osteoarthritis) commonly implicate the finger joints and specifically damage also the layer of articular cartilage. Endeavors are now being made to surgically repair such cartilage lesions biologically using tissue-engineering approaches that draw on donor cells and/or donor tissues. The tendon sheaths, particularly their inner layers, that is, the peritendineum, surround the numerous tendons in the hand. The peritendineum is composed of mesenchymal tissue. We hypothesize that this tissue harbors pluripotent mesenchymal stem cells and thus could be used for cartilage repair, irrespective of the donor’s age. Using a bovine model (young calves vs adult cows), the pluripotentiality of the peritendineal stem cells, namely, their osteogenicity, chondrogenicity, and adipogenicity, was investigated by implementing conventional techniques. Subsequently, the chondrogenic potential of the peritendineal tissue itself was analyzed. Its differentiation into cartilage was induced by the application of specific growth factors (members of the TGF-β-superfamily). The characteristics of the tissue formed were evaluated structurally (immuno) histochemically, histomorphometrically, and biochemically (gene expression and protein level). Our data confirm that the bovine peritendineum contains stem cells whose pluripotentiality is independent of donor age. This tissue could also be induced to differentiate into cartilage, likewise, irrespective of the donor’s age. Preliminary investigations with adult human peritendineal biopsy material derived from the hand’s peritendineal flexor tendon sheaths revealed that this tissue can also be induced to differentiate into cartilage.
Asymmetric, Bilateral Nontraumatic Subperiosteal Orbital Hematomas in an Anticoagulated Patient Following Anesthesia in Prone Positioning
Authors: Kao Brandon W. , Meer Elana A. , Ahmad Meleha T. , Winn Bryan J.
Published: December 2024

The authors report a case of nontraumatic orbital subperiosteal hematoma after general anesthesia with patient in the prone position. The patient, who was on aspirin, clopidogrel, and subcutaneous heparin, presented immediately after sacral ulcer debridement with acute bilateral vision loss and periorbital edema. While the OD improved with conservative management, the OS continued to have 20/200 vision, decreased color vision, afferent pupillary defect, and extraocular movement limitation after lateral canthotomy and cantholysis. Imaging revealed bilateral subperiosteal hematomas in the superior orbital roof stretching the posterior optic nerve. Left orbitotomy with drainage of hematoma under anesthesia was then performed, with full resolution of symptoms and recovery of vision to 20/20 by postoperative week 2. While a few cases of orbital subperiosteal hematoma after nonophthalmic surgeries have been previously reported, the majority were in the supine position, unilateral, and resolved without surgical decompression. This case suggests that the increase in venous pressure from prone positioning, especially in patients on anticoagulation or antiplatelet therapy, could contribute to bleeding into the subperiosteal space. Furthermore, although the orbital compartment syndrome and elevated intraocular pressure resolved with canthotomy/cantholysis, there was persistent compressive optic neuropathy that required surgical intervention.
Development, Content Validity, and Reliability of the Physical Therapy Social Determinants of Health Scale
Authors: Patel Rupal M. , Rethorn Zachary D. , Bjork Elise N.
Published: December 2024

Introduction.

This study describes the development, content validity, and reliability of the Physical Therapy Social Determinants of Health Scale (PT-SDHS), in Doctor of Physical Therapy (DPT) students.

Review of Literature.

Addressing inequities stemming from the social determinants of health (SDOH) is critical for providing effective clinical care and improving population health. Currently, no tool exists to assess DPT students' education or competence with SDOH.

Subjects.

Recruited domain experts were licensed health professionals, had a peer-reviewed publication on SDOH, and had at least 3 years of experience with SDOH. A convenience sample of DPT students was also recruited from multiple cohorts at 2 universities in multiple geographic locations.

Methods.

The Association for Medical Education in Europe best practices for developing questionnaires for educational research guided development of the PT-SDHS. Eight experts established content validity through item- and scale-content validity index measures and modified Kappa statistics. Qualitative data determined clarity and comprehensiveness. Construct validity and scale reliability were determined using exploratory factor analysis and Cronbach's alpha.

Results.

The PT-SDHS showed high item content validity (range: 0.86–1) and scale content validity (S-CVI/UA = 0.83; S-CVI/Ave = 0.98). After expert validation, the PT-SDHS consisted of 30 items with 5 ordinal answer choices. Factor analysis of 254 DPT student responses revealed 4 content domains with a factor loading greater than 0.4. Two items did not load onto any of the factors, and 2 items were cross-loaded onto multiple factors, so they were removed, leaving a scale of 26 items. Cronbach's alpha ranged from 0.74 (satisfactory) to 0.96 (excellent) across the 4 factors.

Discussion and Conclusion.

The PT-SDHS is the first psychometrically valid and reliable instrument related to educating DPT students on 4 SDOH domains: Knowledge, Attitudes, Personal Barriers, and Beliefs About Others. This tool could aid development and assessment of SDOH educational interventions for health care students.
Pan-cancer transcriptomic analysis reveals HSPB8 as a prognostic and immunological biomarker in colorectal cancer
Authors: Deng Yuyong , Sun Xuguang , Jian Rui , Wu Duojia , Wang Junyang , Li Shan
Published: December 2024

Background

Heat shock protein B8 (HSPB8) is implicated in autophagy, and its aberrant expression has been linked to both the initiation and progression of tumors. However, the role and function of HSPB8 in colorectal cancer (CRC) and across multiple cancer types remain unclear. This study aimed to map the transcriptome of autophagy-related genes in CRC and to conduct a pan-cancer analysis of HSPB8 as both a prognostic and immunological biomarker.

Methods

We performed bioinformatics analyses on GSE113513 and GSE74602 to identify differentially expressed genes (DEGs) in CRC. These DEGs were then compared with autophagy-related genes to identify critical overlapping genes. The Kaplan-Meier plotter was used to verify the expression of autophagy-linked DEGs and evaluate its prognostic value. The protein expression of Hub gene in CRC was analyzed using the Human Protein Atlas database. The cBioPortal was used to analyze the type and frequency of Hub gene mutations. The TIMER (Tumor Immune Estimation Resource) database was used to study the correlation between HSPB8 and immune infiltration in CRC.

Results

In total, 825 DEGs were identified, including 8 autophagy-linked DEGs: ATIC, MYC, HSPB8, TNFSF10, BCL2, TP53INP2, ITPR1, and NKX2-3. Survival analysis showed that increased HSPB8 expression significantly correlates with poor prognosis in patients with CRC (p < 0.05). HSPB8 was also found to be differentially expressed in various cancer types, correlating with both prognosis and immune infiltration. Further, changes in HSPB8 methylation and phosphorylation status were observed across several cancers, suggesting potential regulatory mechanisms. Therefore, HSPB8 may serve as a crucial prognostic and immunological biomarker in CRC and other cancers.

Conclusions

This study provides new insights into the role of autophagy-related genes in cancer progression and highlights HSPB8 as a potential target for cancer diagnostics and therapy.
Metabolic Characterization of Deceased Donor Kidneys Undergoing Hypothermic Machine Perfusion Before Transplantation Using 13C-enriched Glucose
Authors: Patel Kamlesh , Nath Jay , Smith Thomas , Darius Tom , Thakker Alpesh , Dimeloe Sarah , Inston Nicholas , Ready Andrew , Ludwig Christian
Published: December 2024

Background.

The provision of a metabolic substrate is one mechanism by which hypothermic machine perfusion (HMP) of kidneys provides clinical benefit. This study aimed to describe de novo metabolism in ex vivo human kidneys undergoing HMP before transplantation using 13C-labeled glucose as a metabolic tracer.

Methods.

Cadaveric human kidneys were perfused with modified clinical-grade perfusion fluid (kidney perfusion solution [KPS-1], Organ Recovery Systems), in which glucose was uniformly enriched with the stable isotope 13C ([U-13C] glucose). The sampled perfusion fluid was analyzed using a blood gas analyzer, and metabolic profiling was performed using 1-dimensional and 2-dimensional nuclear magnetic resonance spectroscopy and mass spectrometry. Functional outcome measures included serum creatinine levels and the development of delayed graft function.

Results.

Fourteen kidneys were perfused with the modified KPS-1 and successfully transplanted. The mean duration of HMP was 8.7 h. There was a sustained increase in the conversion of glucose into de novo glycolytic end products, such as lactate, in donor kidneys during HMP. There was no significant association between functional outcomes and metabolism during the HMP. De novo anaerobic metabolism was indicated by continuing lactate production, as indicated by increasing concentrations of universally 13C-labeled lactate ([U-13C] lactate) in perfusion fluid from all kidneys. This was more evident in donation after circulatory death donor kidneys.

Conclusions.

Our study is the first to use [U-13C] glucose to describe the metabolism during HMP. The consequences of an initial warm ischemic insult on circulatory death in donor kidneys continue during the preservation period.
Midbrain dopamine drives splenic immunity through a brain-to-body circuit
Authors: Gopinath Adithya , Apicella Alfonso , Smith Aidan , Bertero Alice , Freedman Elijah , Hornstein Lauryn , Wood Logan , Ciupe Hannah , Booth Delaney , Campos Sabrina , Soundara Nirvana , Purich Daniel L. , Trevizan-Baú Pedro , Reznikov Leah R. , Urs Nikhil , Guryanova Olga , Wesson Daniel W. , Khoshbouei Habibeh
Published: December 2024

Midbrain dopamine neurons are well-known to shape central nervous system function, yet there is growing evidence for their influence on the peripheral immune systems. Here we demonstrate that midbrain dopamine neurons form a circuit to the spleen via a multisynaptic pathway from the dorsal vagal complex (DVC) through the celiac ganglion. Midbrain dopamine neurons modulate the activity of D1-like and D2-like dopamine receptor-expressing DVC neurons.In vivoactivation of midbrain dopamine neurons induced dopamine release in the DVC and increased immediate early gene expression in both the DVC and celiac ganglion, indicating enhanced neuronal activity. Activation of this midbrain-to-spleen circuit reduced spleen weight and decreased naïve CD4+T-cell populations without affecting total T-cell numbers. These findings unveil a functional midbrain-DVC-celiac ganglion-spleen pathway, through which midbrain dopamine neurons modulate splenic immunity. These novel insights into the neural regulation of the immune system have important implications for diseases involving altered dopamine neurotransmission and highlight potential targets for immunotherapeutic interventions.
The effect of illumination cues on color constancy in simultaneous identification of illumination and reflectance changes
Authors: Virtanen Lari S , Olkkonen Maria , Saarela Toni P
Published: December 2024

To provide a stable percept of the surface color of objects, the visual system needs to account for variation in illumination chromaticity. This ability is called color constancy. The details of how the visual system disambiguates effects of illumination and reflectance on the light reaching the eye are still unclear. Here we asked how independent illumination and reflectance judgments are of each other, whether color constancy depends on explicitly identifying the illumination chromaticity, and what kinds of contextual cues support this identification. We studied the simultaneous identification of illumination and reflectance changes with realistically rendered, abstract 3D-scenes. Observers were tasked to identify both of these changes between sequentially presented stimuli. The stimuli included a central object whose reflectance could vary, and a background that only varied due to changes in illumination chromaticity. We manipulated the visual cues available in the background: local contrast and specular highlights. Identification of illumination and reflectance changes was not independent: While reflectance changes were rarely mis-identified as illumination changes, illumination changes clearly biased reflectance judgments. However, correct identification of reflectance changes was also not fully dependent on correctly identifying the illumination change: Only when there was no illumination change in the stimulus did it lead to better color constancy, that is, correctly identifying the reflectance change. Discriminability of illumination changes did not vary based on available visual cues, but discriminability of reflectance changes was improved with local contrast, and to a lesser extent with specular highlights, in the stimulus. We conclude that a failure of color constancy does not depend on a failure to identify illumination changes, but additional visual cues still improve color constancy through better disambiguation of illumination and reflectance changes.
Grid cells anticipate the animal’s future movement
Authors: Csordás Dóra Éva , Nagele Johannes , Stemmler Martin , Herz Andreas V. M.
Published: December 2024

Grid cells in the rodent medial entorhinal cortex preferentially fire spikes when the animal is within certain regions of space. When experimental data are averaged over time, spatial firing fields become apparent. If these firing fields represented only the current position of the animal, a grid cell’s firing should not depend on whether the animal is running into or out of a firing field. Yet many grid cells are sensitive to the animal’s direction of motion relative to the firing-field center. Such apparent egocentric "inbound-outbound tuning" could be a sign of prospective encoding of future position, but it is unclear whether grid cells code ahead in space or in time. To investigate this question, we decided to undo the inbound-outbound modulation by shifting all spikes within a given firing field by a fixed distance in space or in time. For grid-cell data recorded in mice, optimizing in space requires a forward shift of around 2.5 cm, whereas optimizing in time yielded a forward shift of about 170 ms. In either case the firing-field sizes decrease. Minimizing just the field size yields somewhat smaller shifts (roughly 1.8 cm and around 115 ms ahead). Jointly optimizing along the temporal and spatial dimension reveals a continuum of flat inbound-outbound tuning curves and a shallow minimum for field sizes, located at about 2.3 cm and 35 ms. These findings call into question a purely spatial or purely temporal interpretation of grid-cell firing fields and inbound-outbound tuning.
WITHDRAWN: Leveraging computational tools to understand the triptolide-XPB interaction
Authors: Gorrie David
Published: December 2024

Withdrawal Statement

The authors have withdrawn this manuscript because authorship disputes must be resolved. Therefore, the authors do not wish this work to be cited as a reference for the project. If you have any questions, please contact the corresponding author.
Genetic Causes of Sudden Cardiac Arrest in the Community
Authors: Kransdorf Evan P. , Mathias Marco , Nakamura Kotoka , Tyrer Jonathan , Pharaoh Paul D. , Chugh Harpriya , Reinier Kyndaron , Akdemir Zeynep , Boerwinkle Eric , Yu Bing , Chugh Sumeet S.
Published: December 2024

Background

Annually 300,000 Americans experience sudden cardiac arrest (SCA). Studies in referral SCA cohorts have observed rare variants in genes associated with arrhythmia and cardiomyopathy. We sought to: (1) establish the population prevalence of rare disease-causing variants in a set of candidate genes and (2) confirm the association of disease-causing variants in these genes with SCA in two prospective population-based studies.

Methods

SCA patients (n=3264) were accrued from the Oregon Sudden Unexpected Death Study and the PREdiction of Sudden death in mulTi-ethnic cOmmunities (PRESTO) study and compared to control patients (n=13713) from the Atherosclerosis Risk in Communities (ARIC) study. Whole genome sequencing was performed. Disease-causing (likely pathogenic or pathogenic) variants in candidate genes associated with arrhythmia/cardiomyopathy were identified using updated American College of Medical Genetics and Genomics criteria. Gene- collapsing case-control analysis was performed using the conditional logistic regression-sequence kernel association test.

Results

We identified 300 disease-causing variants, the majority of which were in cardiomyopathy genes (71%). There were 136 patients (4.2%) in the SCA group and 351 patients (2.6%) in the control group with one or more disease-causing variants (OR 1.66, 95% confidence interval 1.33-2.07, p<0.001). We identified 13 genes associated with an increased risk of SCA, nine associated with cardiomyopathy (BAG3, DSC2, DSG2, FLNC, LMNA, MYBPC3, TNNI3, TNNT2, TTN) and four with arrhythmia (CACNA1C, CASQ2, KCNH2, KCNQ1).

Conclusions

Disease-causing variants in cardiomyopathy genes were the predominant genetic cause of SCA. These findings inform which genes to include in genetic screening for SCA.
Modulation of the JAK2-STAT3 pathway promotes expansion and maturation of human iPSCs-derived myogenic progenitor cells
Authors: Caputo Luca , Stamenkovic Cedomir , Tierney Matthew T. , Falzarano Maria Sofia , Bassel-Duby Rhonda , Ferlini Alessandra , Olson Eric N. , Puri Pier Lorenzo , Sacco Alessandra
Published: December 2024

Generation ofin vitroinduced pluripotent cells (hiPSCs)-derived skeletal muscle progenitor cells (SMPCs) holds great promise for regenerative medicine for skeletal muscle wasting diseases, as for example Duchenne Muscular Dystrophy (DMD). Multiple approaches, involving ectopic expression of key regulatory myogenic genes or small molecules cocktails, have been described by different groups to obtain SMPC towards cell-transplantationin vivoas a therapeutic approach to skeletal muscle diseases. However, hiPSCs-derived SMPC generated using transgene-free protocols are usually obtained in a low amount and resemble a more embryonal/fetal stage of differentiation. Here we demonstrate that modulation of the JAK2/STAT3 signaling pathway during anin vitroskeletal muscle differentiation protocol, increases the yield ofPAX7+andCD54+SMPCs and drive them to a post- natal maturation stage, in both human ES and patient-derived iPSCs. Importantly, upon removal of the inhibition from the cultures, the obtained SMPCs are able to differentiate into multinucleated myotubesin vitro.These findings reveal that modulation of the JAK2/STAT3 signaling pathway is a potential therapeutic avenue to generate SMPCsin vitrowith increase potential for cell-therapy approaches.
“Imaging Translation in Early Embryo Development”
Authors: Bensidoun Pierre , Verbrugghe Morgane , Lagha Mounia
Published: December 2024

The ultimate output of gene expression is to ensure that proteins are synthesized at the right levels, locations, and timings. Recently different imaging-based methods have been developed to visualize the translation of single mRNA molecules. These methods rely on signal amplification with the introduction of an array of a short peptide sequence (a tag such as SunTag), recognized by a genetically encodable single-chain antibody (a detector such as scFv). In this chapter, we discuss such methods to image and quantify translation dynamics in the earlyDrosophilaembryo and provide examples based on atwist-32XSunTagreporter. We outline a step-by-step protocol to light-up translation in living embryos. We also detail a combinatorial strategy in fixed samples (smFISH-IF), allowing to distinguish single mRNA molecules engaged in translation.
The impact of sex differences on perceived pain intensity in pain protocol standardization
Authors: Wragan Max , O’Connor Niamh , Ashe Hannah , O’Flaherty Ruairi , Witney Alice G.
Published: December 2024

Background

Sex differences have been widely demonstrated in both acute and chronic pain. Sex differences may have wider impact on research design and analysis than already established. This study addresses an important methodological aspect with regards to how sex differences could influence the design of standardized experimental pain protocols used to characterize an individuals’ pain response.

Methods

This study addresses sex differences of perceived pain at tonic heat pain threshold (HPT). Participants used a computerized visual analogue scale (CoVAS) to continually rated subjective pain intensity during tonic HPT. Metrics (Mean, Standard Deviation, Maximum) were extracted from the CoVAS to characterize perceived pain.

Results

Female participants rated pain intensity at HPT significantly lower than male participants across all extracted metrics used to characterize the coVAS rating. The effect of sex on the mean and standard deviation of pain intensity ratings at HPT was medium, while the effect size of sex on the maximum pain intensity rating at HPT was large.

Conclusion

The significant sex differences in perceived pain intensity at HPT indicates that methods of standardization to a specific pain intensity merit sex-specific consideration. Additionally, these observed sex differences underscore the necessity for sex specific design across both pre-clinical and clinical studies of pain.
A new class of natural anthelmintics targeting lipid metabolism
Authors: Zahreddine Fahs Hala , Refai Fathima S. , Gopinadhan Suma , Moussa Yasmine , Gan Hin Hark , Hunashal Yamanappa , Battaglia Gennaro , Cipriani Patricia G. , Ciancia Claire , Rahiman Nabil , Kremb Stephan , Xie Xin , Pearson Yanthe E. , Butterfoss Glenn L. , Maizels Rick M. , Esposito Gennaro , Page Antony P. , Gunsalus Kristin C. , Piano Fabio
Published: December 2024

Parasitic helminths are a major global health threat, infecting nearly one-fifth of the human population and causing significant losses in livestock and crops. Resistance to the few anthelmintic drugs is increasing. Here, we report a set of avocado fatty alcohols/acetates (AFAs) that exhibit nematocidal activity against four veterinary parasitic nematode species:Brugia pahangi,Teladorsagia circumcinctaandHeligmosomoides polygyrus, as well as a multidrug resistant strain (UGA) ofHaemonchus contortus.AFA shows significant efficacy inH. polygyrusinfected mice. InC. elegans, AFA exposure affects all developmental stages, causing paralysis, impaired mitochondrial respiration, increased reactive oxygen species production and mitochondrial damage. In embryos, AFAs penetrate the eggshell and induce rapid developmental arrest. Genetic and biochemical tests reveal that AFAs inhibit POD-2, encoding an acetyl CoA carboxylase, the rate-limiting enzyme in lipid biosynthesis. These results uncover a new anthelmintic class affecting lipid metabolism.
Nonuple atg8 mutant provides genetic evidence for functional specialization of ATG8 isoforms inArabidopsis thaliana
Authors: Del Chiaro Alessia , Grujic Nenad , Zhao Jierui , Papareddy Ranjith Kumar , Gao Peng , Ma Juncai , Lofke Christian , Bhattacharya Anuradha , Gruetzner Ramona , Bourguet Pierre , Berger Frédéric , Kang Byung-Ho , Marillonnet Sylvestre , Dagdas Yasin
Published: December 2024

Autophagy sustains cellular health by recycling damaged or excess components through autophagosomes. It is mediated by conserved ATG proteins, which coordinate autophagosome biogenesis and selective cargo degradation. Among these, the ubiquitin-like ATG8 protein plays a central role by linking cargo to the growing autophagosomes through interacting with selective autophagy receptors. Unlike most ATG proteins, the ATG8 gene family is significantly expanded in vascular plants, but its functional specialization remains poorly understood. Using transcriptional and translational reporters inArabidopsis thaliana, we revealed that ATG8 isoforms are differentially expressed across tissues and form distinct autophagosomes within the same cell. To explore ATG8 specialization, we generated the nonupleΔatg8mutant lacking all nine ATG8 isoforms. The mutant displayed hypersensitivity to carbon and nitrogen starvation, coupled with defects in bulk and selective autophagy as shown by biochemical and ultrastructural analyses. Complementation experiments demonstrated that ATG8A could rescue both carbon and nitrogen starvation phenotypes, whereas ATG8H could only complement carbon starvation. Proximity labeling proteomics further identified isoform-specific interactors under nitrogen starvation, underscoring their functional divergence. These findings provide genetic evidence for functional specialization of ATG8 isoforms in plants and lay the foundation for investigating their roles in diverse cell types and stress conditions.