bluuebunny/crossref_metadata_2025 huggingface dataset:
(117) RETROSPECTIVE EVALUATION OF POST-SURGICAL ORCHALGIA IN MEN UNDERGOING NO-SCALPEL VASECTOMY
Authors: Morra M , Dhillon H , Nayak J , Patel P
Published: December 2024

Introduction

Vasectomy is a form of permanent contraception in men that is safe, effective, and widely utilized. While complications are relatively uncommon, patients may experience post-vasectomy pain syndrome (PVPS) postsurgically. Current literature quotes a broad range in the incidence of chronic orchalgia following no-scalpel vasectomy from 0.6% - 26%. Chronic scrotal pain associated with a negative impact on quality of life, occurs after vasectomy in about 1-2% of men. Current guidelines state that few of these men require additional surgery, but there is scarce data on the actual proportion of men who will go on to receive surgical treatment for pain.

Objective

We sought to evaluate our incidence of post vasectomy pain as well as the rate of surgical management of post vasectomy pain with the objective of better counselling patients on the risks of vasectomy and subsequent surgeries.

Methods

A chart review was performed for all men who underwent a vasectomy at the Men's Health Clinic during a 20-month period. Their baseline characteristics were collected including age, previous scrotal surgery and history of orchalgia. The presence of pain or complications was collected at a 3 month follow up appointment. Patients with pain were then followed every 6-8 weeks for continued management.

Results

A total of 350 men underwent elective no scalpel vasectomy during this period, with a median age of 37. The majority of patients had no previous history of orchalgia (98%), or history of previous scrotal surgery (94%) and there was no association between these variables on post vasectomy pain. At 3 months post vasectomy, 38/350 (11%) of patients had ongoing pain, while 89% did not report post-operative issues or pain. There was no statistical difference in age between both groups. Semen analysis was only completed by 227/350 (65%) of patients, with 96% of those patients azoospermic. One patient has required surgery (epididymectomy) for management of post vasectomy pain 3 months following vasectomy and now has complete resolution of his pain.

Conclusions

Our retrospective analysis of 350 men who underwent no scalpel vasectomy shows a significant proportion of post vasectomy pain of some degree at the 3-month follow-up appointment, although most cases are resolving or minor and only one patient has required surgical management. This data highlights the importance of counselling men undergoing vasectomy regarding the risks of post procedure orchalgia and the small proportion of men who will require additional surgical intervention.

Disclosure

No.
(124) SUBFERTILITY RISK IN MALE SIBLINGS OF PEDIATRIC BILATERAL INGUINAL SURGERY PATIENTS
Authors: Langston D , Slade A , Malhotra N , Schaeffer A , Hotaling J , Lau G
Published: December 2024

Introduction

Cryptorchidism, a condition linked to male infertility, often presents with bilateral undescended testicles in about 10% of cases. While surgery aims to preserve fertility, genetic predispositions to sub-fertility among brothers of those who had pediatric bilateral inguinal surgery remain under explored.

Objective

In this study, we compared fertility outcomes between males who had bilateral inguinal surgery for hernias or undescended testes and their brothers, hypothesizing a higher sub-fertility risk among brothers of pediatric bilateral orchiopexy patients.

Methods

A statewide database that combines demographic, medical, and residential data for over 90% of the state's pediatric population was used. Our cohort were patients who underwent B/L IHR or BO prior to age 18, and their brothers born within 10 years of the B/L IHR or BO cases. A logistic regression model with clustering on family was performed to assess the likelihood for male siblings to develop male factor infertility controlling for time in Utah since 1996, infertility in the spouse, or unidentified partner data. A mixed-effect Poisson regression with the same parameters was used to assess the number of children in each group.

Results

1019 B/L IHR siblings (627 cases), 360 BO siblings (221 cases), were identified from 1996-2022. The BO sibling cohort was majority white (93.6%), non-Hispanic (74.5%), and 32.5% of the cohort had at least 1 child. Regression analysis revealed brothers of BO patients had a higher likelihood of infertility (2.2% vs. 0.4% IHR-brother, P = 0.004) and their odds of infertility trended towards a higher likelihood (HR = 0.73, [0.3-2.0], P = 0.5) when compared to B/L IHR-brother (HR = 0.2, [0.1-0.6], P = 0.004). While not statistically significant for the BO cohort, this would suggest a trend towards a genetic association.

Conclusions

BO shows a genetic influence on sub-fertility, with increased infertility diagnoses among male siblings versus B/L IHR. Conversely, male siblings of B/L IHR patients exhibit significantly lower infertility rates, suggesting surgery-related factors predominate in adulthood infertility diagnoses post-pediatric B/L IHR.

Disclosure

Any of the authors act as a consultant, employee or shareholder of an industry for: StreamDx, Inherent Bioscience, Turtle Health, Maimus, Carrot Fertility.
(139) THE ARTIFICIAL URINARY SPHINCTER IMPROVES DEPRESSION, ANXIETY AND OVERALL EMOTIONAL HEALTH IN MEN WITH STRESS URINARY INCONTINENCE; ANALYSIS OF THE ARTIFICIAL URINARY SPHINCTER CLINICAL OUTCOMES TRIAL (AUSCO)
Authors: Peterson A , Wood H , Chaussee E , Elliott S , Vanni A , Jones L , Broghammer J , Henry G , Breyer B , Erickson B , Burnett A , Terlecki R , Johnsen N , Chan L , Meyer J , Flynn B , Khavari R , Rainbow K , Smith T , Kaufman M
Published: December 2024

Introduction

The artificial urinary sphincter (AUS) has been available for over 50 years with excellent outcomes for the treatment of male stress urinary incontinence (SUI). However, few reports focus on the effects an AUS may have on mental health in men with SUI.

Objective

We examined the effects on depression, anxiety and overall emotional health in patients treated for SUI with the AUS.

Methods

The Artificial Urinary Sphincter Clinical Outcomes Trial (AUSCO) is a single-arm, prospective, multi-center study designed to evaluate objective and subjective outcomes of men with SUI treated with the AMS 800 AUS. This was approved by each institutional committee on ethics in human investigation (NCT04088331). A total of 115 subjects were implanted at 17 sites. Subjects served as their own controls and follow-up assessments at 3-, 6-, and 12-months post device activation were compared to baseline values. The Incontinence QoL (IQoL), Incontinence Impact Questionnaire (IIQ-7), and EQ-5D-5L were administered at these intervals.

Results

Of the 115 implanted subjects, 100 completed QoL assessments at 12 months as of May 2024. Depression rating (Item 5, IQoL) significantly improved from baseline to 12 months, with 85% (85/100) of patients reporting feeling at least “a little” depressed at baseline decreasing to 39% (39/100) at 12 months (p < 0.0001). Emotional health rating (Item 6, IIQ-7) also improved, with 16% (16/100) patients reporting being “greatly” affected by incontinence at baseline decreasing to 3% (3/100) at 12 months (p < 0.0001). The anxiety/depression domain on the EQ-5D-5L (Item 5) was also significantly improved, with 50% (50/100) of patients reporting being at least “slightly” anxious or depressed at baseline decreasing to 30% (30/100) at 12 months (p = <0.0001) (Table).

Conclusions

The AUS has been commonly referred to as the “gold standard” for treatment of men with stress urinary incontinence for over half a century. While multiple reports focus on improvement in volume of leakage, fewer concentrate on quality of life with emphasis on its effects on depression and related mental health scores. This data clearly demonstrates that treatment of SUI in patients with the AUS improves depression symptoms and anxiety for these patients.

Disclosure

Yes, this is sponsored by industry/sponsor: Boston Scientific.

Clarification: Industry initiated, executed and funded study.

Any of the authors act as a consultant, employee or shareholder of an industry for: Boston Scientific.
Effect of pelvic arterial stenosis on erectile function: determining the severity threshold for erectile dysfunction
Authors: Huang Wei-Lun , Tung Sheng-Yung , Tseng Chi-Shin , Wang Tzung-Dau , Lee Wen-Jeng , Chen Jyh-Horng , Su Yann-Ron , Chang Hong-Chiang , Chang Yi-Kai
Published: December 2024

Background

Pelvic arterial (PLA) stenosis is associated with arterial insufficiency of the penis and erectile dysfunction (ED), but the effect of different severities of PLA stenosis on ED remains unclear.

Aim

To investigate how different severities of PLA stenosis affect erectile function.

Methods

We included patients who visited our clinic for ED and underwent computed tomography angiography (CTA) and dynamic duplex sonography (DUS). The erectile hardness score (EHS), simplified International Index of Erectile Function (IIEF-5), DUS and CTA results, and flow index (FI) calculated from the peak systolic velocity (PSV) and PLA stenosis percentages were analyzed. EHS < 3 was defined as significant ED. PLA stenosis was analyzed by the mean PLA (average of the right and left PLA) and unilateral or bilateral stenoses. According to severity, stenosis was classified as mild, moderate, or severe.

Outcomes

Subjective and objective parameters, including the IIEF-5 score, EHS, PSV, and FI, in relation to different severities of PLA stenosis.

Results

The study included 182 patients. Vascular parameters such as the mean PSV, PLA stenosis, and FI correlated with EHS and IIEF-5 scores. Receiver operating characteristic analyses for predicting EHS ≥ 3 showed that all vascular parameters had acceptable discriminatory ability. During the analysis performed using the mean PSA stenosis, EHS decreased in patients with mild and severe mean PLA stenosis, although a PSV drop was noted only in severe cases. The proportion achieving EHS 3 significantly dropped in patients with at least mild mean PLA stenosis. Using unilateral or bilateral PLA stenosis, the EHS significantly dropped in patients with severe unilateral and bilateral PLA stenosis, with PSV decreasing on the affected side in severe unilateral stenosis. However, the mean PSV did not drop despite different unilateral stenosis severities. The proportion achieving EHS 3 significantly dropped among patients with at least moderate unilateral PLA stenosis and bilateral PLA stenosis but not in mild unilateral cases.

Clinical Implications

The severity of PLA stenosis is correlated with the risk of ED.

Strengths & Limitations

The strength of this study lies in its analysis of the effect of PLA stenosis on erectile function from various perspectives, including unilateral, bilateral, and mean stenosis. However, the absence of validation regarding the outcomes of endovascular therapy is a limitation.

Conclusion

Mild mean PLA stenosis and moderate unilateral PLA stenosis are associated with increased risks of ED; however, mild unilateral PLA stenosis does not affect erectile function.
Military Nurses’ Deployment Experiences: A Qualitative Metasynthesis
Authors: Christiansen Mollie F , Tice Whitney , Kessinger Stephanie , Coats Heather
Published: December 2024

Introduction

Military medical personnel, including nurses, face a wide array of emotional and psychological issues while deployed. Understanding the challenges military nurses face in the deployed setting may prove useful in effectively preparing nurse leaders for future disaster responses in the military and civilian sectors. The purpose of this metasynthesis is to answer the following research question: What are the experiences of U.S. military and allied nurses deployed to medical facilities in combat operations and support areas since 9/11/2001?

Methods

A qualitative metasynthesis was conducted to determine commonality of combat-related deployment experiences for U.S. military and allied nurses. After development of the research question, this metasynthesis included 4 steps: (1) perform structured literature search, (2) critical appraisal, (3) reciprocal translation, and (4) synthesize findings. Studies were limited to the years 2004-2023 to focus the search on Operation Enduring Freedom and Operation Iraqi Freedom-related deployments. Reference review of studies retrieved through database search also contributed to the final sample. Screening criteria included: (1) qualitative or mixed methods studies, (2) sample comprised of U.S. or allied country medical/nursing personnel, and (3) care primarily occurring in a fixed facility located in Iraq, Afghanistan, or Kuwait. Studies focusing on reintegration after deployment or air evacuation personnel/nonfixed facility settings were excluded. A total of 11 studies met inclusion criteria. Critical appraisal was conducted on all studies. Data analysis utilized an inductive and iterative process. Reciprocal translation and meta-ethnographic techniques were used to identify words/phases that contained significant meaning and to identify themes/subthemes. Themes formed that described commonalities across nurses’ experiences.

Results

Three primary themes arise from critical examination of military nurses’ deployment experiences: (1) “care in a combat zone,” (2) “leadership in a combat zone,” and (3) “personhood.” The subthemes address experiences or concerns related to an individual participant’s role as a “care giver,” “leader,” or “person.” The 3 themes formed by this qualitative metasynthesis represent a holistic view of a military nurse in a deployed setting.

Conclusions

Military nurses’ deployment experiences relate to their multiple role(s) as a clinician, officer, and human being. By better understanding military nurses’ past deployment experiences and related themes, nurse leaders and individuals can better prepare for supporting staff in future combat operations. The complexities of “caring,” “leading,” and “personhood” may contribute to emotional distress among deployed military medical personnel.
Seronegative rheumatoid arthritis found in an 85-year-old woman during preoperative investigations for knee replacement surgery for osteoarthritis
Authors: Nakano Haruka , Hirao Makoto , Kim Dong Seop , Okamura Gensuke , Hoshida Yoshihiko , Noguchi Takaaki , Etani Yuki , Ebina Kosuke , Okada Seiji , Hashimoto Jun , Ohshima Shiro
Published: December 2024

This report describes the case of an 85-year-old woman who was found to have seronegative rheumatoid arthritis during preoperative investigations for knee replacement surgery for osteoarthritis. Follow-up for knee osteoarthritis was continued for many years without any symptoms involving other joints. Before total knee arthroplasty for osteoarthritis, preoperative investigations revealed a highly inflammatory state. After differential diagnosis, seronegative rheumatoid arthritis was diagnosed. Even in preoperative investigations before total knee arthroplasty for very old patients with osteoarthritis, the possibility of rheumatoid arthritis developing should always be kept in mind.
A chimeric RNA consisting of siRNA and aptamer for inhibiting dengue virus replication
Authors: Amano Ryo , Takahashi Masaki , Haga Kazumi , Yamamoto Mizuki , Goto Kaku , Ichinose Akiko , Hamada Michiaki , Gohda Jin , Inoue Jun-ichiro , Kawaguchi Yasushi , Moi Meng Ling , Nakamura Yoshikazu
Published: December 2024

Silencing viruses by chimeric RNAs, wherein small interfering RNAs (siRNAs) targeting viral RNAs are conjugated with RNA aptamers specific to viral envelope proteins, is a promising treatment for viral infection diseases; however, practical evaluations are apparently lacking. Here, we present a chimeric RNA comprises siRNA and RNA aptamer, both of which target all four serotypes of dengue virus (DENV), for suppressing DENV replication. The siRNA targeting consensus sequences in the 3′-UTR of all four DENV serotypes suppressed the expression of a reporter gene carrying the siRNA-targeted sequence of DENV-1 by ∼70%. The RNA aptamer generated by VLP-SELEX using DENV-1-VLPs as baits showed an affinity for all four DENV-VLP serotypes, presumably without affecting the fusion process. After conjugation of each modality, the chimeric RNA significantly suppressed authentic DENV-1 and DENV-2 production in vitro. Our study provides evidence that chimeric RNA is a potentially effective antiviral agent.
Current Trends in the Allocation of NIH Funding of Brain Tumor Research
Authors: Nawabi Noah L A , Saway Brian F , Jha Rohan , Pereira Matheus , Mehta Neel , Das Arabinda , Zukas Alicia , Lindhorst Scott , Strickland Ben A
Published: December 2024

Background

The National Institute of Health (NIH) provides a sizable annual budget towards brain tumor research. However, funding allocation for specific pathologies remains poorly described. We aimed to characterize the current landscape of NIH funding towards brain tumors as a function of pathology.

Methods

NIHRePORTER was queried to identify studies focused on glioblastoma, pediatric glioma, oligodendroglioma, brain metastasis, meningioma, pituitary adenoma, and vestibular schwannoma, from 2000-2023. Studies with R, U and P funding mechanisms were included. Data was compiled and assessed according to pathology.

Results

Across these 7 tumors, 3,320 unique studies with R, U, or P funding mechanisms were identified from 2000-2023. These were conducted across 480 unique institutions. The sum of funds allocated to all studies was $1,607,662,631. Glioblastoma commanded the largest portion of funds, representing 54% of R mechanisms, 55% of R01-funded studies, 48% of U mechanisms, and 49% of P mechanisms, and accounted for 51% ($813,556,423) of total funding. Brain metastasis was the second most-funded tumor, representing 31% of all R mechanisms, 31% of all R01-funded studies, 26% of all U mechanisms, and 28% of all P mechanisms, and accounted for 29% ($472,715,745) of funding. The remaining 14% of R mechanisms, 26% of U mechanisms, and 23% of P mechanisms focused on the remaining pathologies, and accounted for 20% ($321,390,463) of funding.

Conclusions

The current landscape of NIH funding for brain tumor research indicates awarded mechanisms prioritize malignant intra-axial malignancies. Despite their prevalence, skull base neoplasia are far less represented in NIH funded studies.
A scoping review of diffuse hemispheric glioma, H3 G34-mutant: Epigenetic and molecular profiles, clinicopathology, and treatment avenues
Authors: Tang Kayen , Cesaire Melissa , McDonald Taylor , Cimino Patrick J , Castro Maria G , Jackson Sadhana
Published: December 2024

Background

Survival of pediatric and young adults with malignant glioma remains poor despite progress in treatment. This is especially true for diffuse hemispheric glioma (DHG), H3 G34-mutant, which is often present in adolescent and young adult patients. This scoping review consolidates existing knowledge of DHG H3 G34-mutant and identifies future targets and therapeutic options. By streamlining this information, we aim to elucidate knowledge gaps in the field to better inform the community and motivate future research efforts.

Methods

In October 2024, MEDLINE, Embase, Cochrane Library, and Web of Science Core Collection were searched. Two reviewers screened all articles by title and abstract review and 3 independent reviewers extracted all studies meeting inclusion criteria relevant to H3G34R/V tumors (preclinical and clinical studies).

Results

Of the 2203 articles screened, 220 were deemed eligible (79 literature reviews, 7 systematic reviews, 63 preclinical studies, and 71 clinically oriented studies). We found that the United States and Acta Neuropathologica were the top country and journal contributors, respectively.

Conclusion

For this disease, it is critical to the field to conduct further research related to complexities of the tumor microenvironment, translation of preclinical studies to therapeutic early phase trials, and determining the role of targeted central nervous system drug delivery, so as to improve disease prognosis and survival.
Immunocompetent murine glioblastoma stem-like cell models exhibiting distinct phenotypes
Authors: Kardani Kimia , Ghouse Shanawaz M , Din Abdul Jabbar Muzammil Arif , Rajasubramanian Namita , Sanchez Gil Judit , Stemmer-Rachamimov Anat , Soda Yasushi , Martuza Robert L , Hara Toshiro , Wakimoto Hiroaki , Rabkin Samuel D
Published: December 2024

Background

Glioblastoma (GBM) treatment is hindered by a dearth of representative mouse GBM preclinical models in immunocompetent mice. Here, we characterized 5 murine GBM stem-like cell (mGSC) models derived from lentivirus-induced tumors in transgenic mice that are driven by the activation of the Nf1-Ras signaling pathway and inactivation of Tp53.

Methods

MGSC lines (005, RIG, NF53, C1, and C3) were cultured as spheres in serum-free stem cell media. Whole exome sequencing (WES) was employed to quantify single nucleotide polymorphisms (SNPs). Stem cell properties were characterized by stemness in vitro and tumorigenicity after intracerebral implantation in C57BL/6 mice. Tumor phenotypes and the immune microenvironment were characterized by immunohistochemistry, flow cytometry, and RNA sequencing.

Results

WES revealed a large variation in coding sequence SNPs across mGSC lines (~20-fold), likely influenced by the mixed backgrounds of the parental mice. MGSCs exhibited variable clonogenic sphere formation and CD133 expression levels. In vivo, they consistently initiated lethal malignant gliomas, with median survival ranging from 29 to 82 days, and showed strong CD44 expression and variable invasiveness. The tumor microenvironment featured an abundance of CD68+ macrophages and uniform high PD-L1+ myeloid cells, while T-cell infiltration varied among the models, with low mutation burden C1 and C3 exhibiting fewer tumor-infiltrating T cells.

Conclusions

Upon orthotopic implantation in immunocompetent mice, mGSCs generate tumors characteristic of human GBM. Despite similar strategies to generate these mGSCs, they exhibited a range of phenotypes and immune profiles in mGSC-derived orthotopic tumors. These mGSCs provide new preclinical GBM models for developing GBM immunotherapies.
Above-Curie-temperature ultrafast terahertz emission and spin current generation in a 2D superlattice (Fe3GeTe2/CrSb)3
Authors: Li Peiyan , Wu Na , Liu Shanshan , Cheng Yu , Gong Piming , Tong Junwei , Liu Jianan , He Wei , Xiu Faxian , Zhao Jimin , Meng Sheng , Wu Xiaojun
Published: December 2024

The increasing demand for denser information storage and faster data processing has fueled a keen interest in exploring spin currents up to terahertz (THz) frequencies. Emergent 2D intrinsic magnetic materials constitute a novel and highly controllable platform to access such femtosecond spin dynamics at atomic layer thickness. However, the function of 2D van der Waals magnets are limited by their Curie temperatures, which are usually low. Here, in a 2D superlattice (Fe3GeTe2/CrSb)3, we demonstrate ultrafast laser-induced spin current generation and THz radiation at room temperature, overcoming the challenge of the Curie temperature of Fe3GeTe2 being only 206 K. In tandem with time-resolved magneto-optical Kerr effect measurements and first-principles calculations, we further elucidate the origin of the spin currents—a laser-enhanced proximity effect manifested as a laser-induced reduction of interlayer distance and enhanced electron exchange interactions, which causes transient spin polarization in the heterostructure. Our findings present an innovative, magnetic-element-free route for generating ultrafast spin currents within the 2D limit, underscoring the significant potential of laser THz emission spectroscopy in investigating laser-induced extraordinary spin dynamics.
Is Respiratory Viral Infection an Inciting Event in the Development of Melioidosis? A Systematic Evaluation of Co-infection With Burkholderia pseudomallei and SARS-CoV-2 or Influenza
Authors: Martin Genevieve E , Chen Jerry L J , Woerle Celeste , Hinchcliff Alexandra , Baird Robert W , Davies Jane , Currie Bart J
Published: December 2024

Respiratory viral infection may increase infection with Burkholderia pseudomallei progressing to clinical disease (melioidosis). This data linkage study evaluated associations between melioidosis and SARS-CoV-2 or influenza. Among 160 melioidosis cases, there was no difference in risk factors, vaccine status, or disease severity between 17 with viral co-infection and 143 without.
Boosting transcriptional activities by employing repeated activation domains in transcription factors
Authors: He Chaochao , Liang Yue , Chen Runzhou , Shen Yuxiao , Li Runhui , Sun Tingting , Du Xing , Ni Xiaomei , Shang Junzhong , He Yanhong , Bao Manzhu , Luo Hong , Wang Jihua , Liao Pan , Kang Chunying , Yuan Yao-Wu , Ning Guogui
Published: December 2024

Enhancing the transcriptional activation activity of transcription factors (TFs) has multiple applications in organism improvement, metabolic engineering, and other aspects of plant science, but the approaches remain unclear. Here, we used gene activation assays and genetic transformation to investigate the transcriptional activities of two MYB TFs, PRODUCTION OF ANTHOCYANIN PIGMENT 1 (AtPAP1) from Arabidopsis (Arabidopsis thaliana) and EsMYBA1 from Epimedium (Epimedium sagittatum), and their synthetic variants in a range of plant species from several families. Using anthocyanin biosynthesis as a convenient readout, we discovered that homologous naturally occurring TFs showed differences in the transcriptional activation ability and that similar TFs induced large changes in the genetic program when heterologously expressed in different species. In some cases, shuffling the DNA-binding domains and transcriptional activation domains (ADs) between homologous TFs led to synthetic TFs that had stronger activation potency than the original TFs. More importantly, synthetic TFs derived from MYB, NAC, bHLH, and ethylene-insensitive3-like (EIL) family members containing tandemly repeated ADs had greatly enhanced activity compared to their natural counterparts. These findings enhance our understanding of TF activity and demonstrate that employing tandemly repeated ADs from natural TFs is a simple and widely applicable strategy to enhance the activation potency of synthetic TFs.
Disagreement on foundational principles of biological aging
Authors: Gladyshev Vadim N , Anderson Benjamin , Barlit Hanna , Barré Benjamin , Beck Samuel , Behrouz Bahareh , Belsky Daniel W , Chaix Amandine , Chamoli Manish , Chen Brian H , Cheng Kaiyang , Chuprin Jane , Churchill Gary A , Cipriano Andrea , Colville Alex , Deelen Joris , Deigin Yuri , Edmonds KeHuan K , English Bradley W , Fang Ruogu , Florea Michael , Gershteyn Iosif M , Gill Diljeet , Goetz Laura H , Gorbunova Vera , Griffin Patrick T , Horvath Steve , Borch Jensen Martin , Jin Xin , Jovanovska Sara , Kajderowicz Kathrin M , Kasahara Tomoko , Kerepesi Csaba , Kulkarni Subhash , Labunskyy Vyacheslav M , Levine Morgan E , Libert Sergiy , Lu J Yuyang , Lu Yuancheng Ryan , Marioni Riccardo E , McCoy Brianah M , Mitchell Wayne , Moqri Mahdi , Nasirian Farzaneh , Niimi Peter , Oh Hamilton Se-Hwee , Okundaye Brian , Parkhitko Andrey A , Peshkin Leonid , Petljak Mia , Poganik Jesse R , Pridham Glen , Promislow Daniel E L , Prusisz Weronika , Quiniou Margaux , Raj Ken , Richard Daniel , Ricon Jose Luis , Rutledge Jarod , Scheibye-Knudsen Morten , Schork Nicholas J , Seluanov Andrei , Shadpour Michael , Shindyapina Anastasia V , Shuken Steven R , Sivakumar Sruthi , Stoeger Thomas , Sugiura Ayumu , Sutton Nadia R , Suvorov Alexander , Tarkhov Andrei E , Teeling Emma C , Trapp Alexandre , Tyshkovskiy Alexander , Unfried Maximilian , Ward-Caviness Cavin K , Yim Sun Hee , Ying Kejun , Yunes Jeffrey , Zhang Bohan , Zhavoronkov Alex
Published: December 2024

To gain insight into how researchers of aging perceive the process they study, we conducted a survey among experts in the field. While highlighting some common features of aging, the survey exposed broad disagreement on the foundational issues. What is aging? What causes it? When does it begin? What constitutes rejuvenation? Not only was there no consensus on these and other core questions, but none of the questions received a majority opinion—even regarding the need for consensus itself. Despite many researchers believing they understand aging, their understanding diverges considerably. Importantly, as different processes are labeled as “aging” by researchers, different experimental approaches are prioritized. The survey shed light on the need to better define which aging processes this field should target and what its goals are. It also allowed us to categorize contemporary views on aging and rejuvenation, revealing critical, yet largely unanswered, questions that appear disconnected from the current research focus. Finally, we discuss ways to address the disagreement, which we hope will ultimately aid progress in the field.
Regularization of Matrices in the Covariant Derivative Interpretation of Matrix Models
Authors: Hattori Keiichiro , Mizuno Yuki , Tsuchiya Asato
Published: December 2024

We study regularization of matrices in the covariant derivative interpretation of matrix models, a typical example of which is the type IIB matrix model. The covariant derivative interpretation provides a possible way in which curved spacetimes are described by matrices, which are viewed as differential operators. One needs to regularize the operators as matrices of finite size in order to apply the interpretation to nonperturbative calculations such as numerical simulations. We develop a regularization of the covariant derivatives in two dimensions by using the Berezin–Toeplitz quantization. As examples, we examine the cases of $S^2$ and $T^2$ in detail.
FeMOFs/CO loading reduces NETosis and macrophage inflammatory response in PLA based cardiovascular stent materials
Authors: Xie Yinhong , Chi Mengchen , Yang Xinlei , Dong Ruichen , Yang Ao , Yin Antao , Weng Yajun
Published: December 2024

Modification of polylactic acid (PLA) is a promising strategy for the next generation of bioresorbable vascular stent biomaterials. With this focus, FeMOFs nanoparticles was incorporated in PLA, and then post loading of carbon monoxide (CO) was performed by pressurization. It showed FeMOFs incorporation increased hydrophilicity of the surface and CO loading, and CO release was sustained at least for 3 days. It is well acknowledged NETosis and macrophage mediated inflammation are the principal effectors of atherosclerosis and cardiovascular disease, and it further increases the risk of late stent thrombosis and restenosis. In this study, the effects of CO release of PLA/FeMOFs/CO on NETosis and macrophage behavior were thoroughly explored. In vitro evaluation results showed that PLA/FeMOFs/CO significantly inhibited neutrophil extracellular traps (NETs) release and neutrophil elastase expression by reducing intracellular reactive oxygen species in a simulated inflammatory environment. It reduced Lipopolysaccharide-induced macrophage inflammation with decreased tumor necrosis factor-α expression and increased IL-10 expression. Meanwhile it enhanced endothelial cell activity and growth in inflammatory environment, and inhibited platelet adhesion and activation. In vivo implantation results confirmed that PLA/FeMOFs/CO reduced the macrophages and neutrophils mediated inflammatory response, thus reduced the neointimal hyperplasia. Overall, PLA/FeMOFs/CO effectively prevented the inflammation and restenosis associated with PLA implantation. Our study provides a new strategy to improve the immunocompatibility of PLA implant materials.
The Next Chapter of Big Data in Finance
Authors: Goldstein Itay , Spatt Chester S , Ye Mao
Published: December 2024

The second special issue on big data in finance showcases advancements in research related to data of large size, high dimension, and complex structure since the first NBER/RFS big data conference. The papers published in this next chapter address some questions that were proposed in the initial special issue in 2021. Other papers are more directly connected to recent developments in the markets. We discuss some new research directions, following on the papers published here. They include evaluating market microstructure reforms, understanding medium-frequency trading, improving missing data imputations, and deepening data valuation. We look forward to more developments to follow.
Longitudinal trajectories of the Scleroderma Health Assessment Questionnaire (SHAQ) visual analogue scales: a retrospective cohort study
Authors: Hughes Michael , Sylvestre Yvonne , Manning Joanne , Wragg Elizabeth , Mandzuk Melissa , Samaranayaka Muditha , Dinsdale Graham , Vail Andy , Herrick Ariane L
Published: December 2024

Objective

SSc is disabling. However, the different factors contributing to this disability and how these change over time have been little studied. Our aim was to examine the trajectories over time of the six visual analogue scales (VAS) of the Scleroderma HAQ (SHAQ), associations of disease-related factors with these trajectories, and relationships with overall functional ability.

Methods

This was a retrospective study of data collected prospectively from patients attending a single tertiary centre between 2005 and 2022. VAS (pain, intestinal, breathing, RP, digital ulcers, ‘overall’) were analysed using linear mixed-effects models, and relationships between the six VAS and functional ability [HAQ Disability Index (HAQ-DI)] and scleroderma functional index (FI) by correlating the average gradients obtained from individual linear regressions.

Results

A total of 537 patients with at least two time-points were included, followed for a mean (s.d.) of 6.8 (4.2) years. VAS intestinal scores increased (i.e. worsened) by 0.085 points (95% CI 0.041–0.130, P < 0.001) per year, VAS breathing by 0.056 points (95% CI 0.016–0.096, P = 0.006) and VAS overall scores by 0.073 points (95% CI 0.032–0.114, P = 0.001). The longer the duration between RP onset and SSc diagnosis, the lower the VAS pain and VAS intestinal scores. The odds of having at least one digital ulcer reduced with disease duration, with diffuse cutaneous subtype and with anti-Scl70 positivity. Average gradients for all six VAS scales correlated (albeit variably/weakly) with HAQ-DI and scleroderma FI gradients.

Conclusion

Longitudinal assessment of the six SHAQ VAS, and associations of baseline characteristics with the individual VAS time courses, provide insights into disease trajectory and overall disability.
Catch-up of CoPs in GIS and IVC: evidence from Chinese CNC machine tools
Authors: Liu Wenlan , Guo Dong , Rogers Juan
Published: December 2024

In the era of innovation globalization, realizing technology catch-up poses a challenge to late-coming countries. This paper integrates the conceptual framework of the global innovation system (GIS) and the model of the innovation value chain (IVC) and takes the high-grade computer-numerical-control(CNC) machine tools’ catch-up in China as a case study to analyze the characteristics and mechanisms for the catch-up of complex product systems (CoPs) in different globalization historical stages from the perspective of research and development (R&D), transformation, and commercialization. We find that strengthening the GIS–IVC-based resource integration of innovation for R&D, pilot and demonstration plants, and commercialization is the key factor in promoting the catch-up of CoPs in emerging economies, and effective guidance of innovation policies is essential for promoting the catch-up of CoPs in the global era.
Digital governance and AI: boosting OFDI’s impact on regional innovation performance
Authors: Wang Zhaoxing , Gao Yuchen , Zhou Yuan , Xue Lan
Published: December 2024

In the realm of global innovation, outward foreign direct investment (OFDI) serves as a pivotal channel for firms to integrate into international innovation networks. However, scant research has probed into the impact mechanisms of OFDI on firms’ innovation, particularly in the era of digitization and artificial intelligence (AI). In this study, we investigate OFDI’s effect on regional innovation performance by analysing a panel data of Chinese provinces. We find that OFDI significantly promotes the performance of regional innovation development. Moreover, we also identify two moderating factors, digital governance and AI, which significantly enhance the effect of OFDI on regional innovation performance.
“You just feel re-violated”: coercive sexual control in juvenile detention
Authors: Powell Amber Joy
Published: December 2024

Despite political calls on the state to “protect the children” from sexual violence, feminist scholars argue the state itself reproduces routine gender-based violence toward incarcerated communities, including youth. Building upon this work, I draw from twenty-three life history interviews with formerly incarcerated cis- and transgender men and women survivors to show how carceral norms facilitate a system of coercive sexual control. I define coercive sexual control as the policies, practices, and social relations that create the context for routine sexual violence and institutional harm toward youth. Coercive sexual control includes the sexual degradation of youth bodies, the underground economy of sexual favors, and the institutional denial of sexual harm. A theory of coercive sexual control shifts attention from sexual violence as solely interpersonal and episodic to the broader institutional mechanisms of power and social control that produce sexual exploitation against youth under the carceral state. Centering carceral institutions as sites of endemic sexual violence further unearths crucial discrepancies between institutional claims of prioritizing children’s sexual safety “on the books” and gaslighting youth claims of sexual misconduct in everyday practice.
Partial activation of salt-inducible kinase 3 delays the onset of wakefulness and alleviates hypersomnia due to the lack of protein kinase A-phosphorylation site
Authors: Nakata Shinya , Fujiyama Tomoyuki , Asano Fuyuki , Komiya Haruna , Hotta-Hirashima Noriko , Juichi Motoki , Komine Daiki , Kakizaki Miyo , Ikkyu Aya , Mizuno Seiya , Takahashi Satoru , Miyoshi Chika , Funato Hiromasa , Yanagisawa Masashi
Published: December 2024

Study Objectives

Sleep/wakefulness is regulated by intracellular signaling pathways composed of protein kinases such as salt-inducible kinase 3 (Sik3). Sik3-deficiency in neurons decreases nonrapid eye movement (NREM) sleep time and electroencephalogram (EEG) delta power during NREM sleep, while Sik3Slp mice lacking a protein kinase A (PKA)-phosphorylation site, S551, show hypersomnia phenotype. In this study, we examined how a phosphomimetic mutation of the 221st threonine residue (T221E), which provides a partial (weak) constitutive activity of the kinase, affects sleep/wakefulness and circadian behavior. We also examined the effect of T221E substitution on the hypersomnia phenotype of Sik3Slp mice.

Methods

We examined the sleep/wake behavior of heterozygous and homozygous Sik3T221E mice and Sik3T221E;Slp mice using EEG and electromyogram recording. We also examined the circadian behavior of Sik3T221E mice using a running wheel under the light–dark cycle and constant darkness.

Results

Heterozygous and homozygous Sik3T221E mice showed normal sleep time and sleep homeostatic responses. Homozygous Sik3T221E mice exhibited a delayed onset of wakefulness at the early dark phase and longer circadian periods. Sik3T221E;Slp mice showed decreased NREM sleep time and homeostatic responses compared to Sik3Slp mice.

Conclusions

Our results suggest that the peak onset of wakefulness is sensitive to disturbed kinase activity of SIK3, and the relationship between phosphorylation at T221 and S551 is critical for regulating sleep need.
The association between childhood maltreatment and multidimensional sleep health in adolescents at high risk of emotional and behavioral problems
Authors: Zarchev Milan , Kamperman Astrid M , Hoepel Sanne J W , Hoogendijk Witte J G , Mulder Cornelis L , Grootendorst-van Mil Nina H
Published: December 2024

Study Objectives

Impaired sleep following trauma such as childhood maltreatment is both a prognostic factor for future mental illness and a feasible intervention point. Yet, associations between childhood maltreatment and objectively measured sleep components are rarely found. New approaches advance the use of multidimensional sleep health scores instead of individual sleep components. However, no such methodology has been used to study the consequences of maltreatment on sleep health in adolescent cohorts so far. We hypothesized that childhood maltreatment will be associated with poorer sleep health in adolescence.

Methods

A cross-sectional sample of 494 adolescents at high risk of emotional and behavioral problems (mean age 17.9) completed the Childhood Trauma Questionnaire—Short Form to assess five forms of maltreatment (emotional and physical abuse/neglect and sexual abuse) assessed as continuous sum scores. During nine nights of actigraphy and sleep diary measurements, data on sleep regularity, satisfaction, alertness, timing, efficiency, and duration were collected, which were combined into a sleep health composite score ranging from 0 to 6. Linear regression models were adjusted for age, sex, household income, ethnic origin, educational level, urbanization of living environment, and parental psychopathological problems.

Results

Associations were found between all forms of maltreatment and poorer sleep health (p < .031), except for sexual abuse (p = .224). Partial r effect sizes ranged from −0.12 (95% CI = −0.22 to −0.01) for emotional neglect to −0.18 (−0.28 to −0.08) for total maltreatment.

Conclusions

Maltreatment was associated with impairment in everyday sleep health, reflected in both subjective and objective measurements of sleep.
Insomnia symptoms are associated with return to use and non-fatal overdose following opioid use disorder treatment
Authors: Hochheimer Martin , Ellis Jennifer D , Strickland Justin C , Rabinowitz Jill A , Hobelmann J Gregory , Huhn Andrew S
Published: December 2024

Study Objectives

Opioid use disorder (OUD) is a chronic, relapse-prone condition, often accompanied by sleep disturbances such as insomnia. While sleep disturbances have been implicated in negative treatment outcomes, no large-scale studies have examined the relationship between insomnia disorder and outcomes for persons completing an acute OUD treatment episode. This study assessed the association between insomnia symptoms at treatment intake, during treatment, and following acute treatment with post-treatment episode return to use and non-fatal overdose outcomes.

Methods

This study analyzed data from 1905 individuals with OUD who received one of three forms of acute OUD treatment: supervised withdrawal, intensive outpatient, or residential treatment at 70 programs in the United States in 2021. Insomnia was assessed using the Insomnia Severity Index (ISI). Logistic regression and mixed regression analyses were performed to evaluate the association between insomnia and return to substance use or non-fatal overdose following a treatment episode.

Results

Higher ISI scores at intake were significantly associated with increased odds of return to use one-month post-treatment episode (p-value = .006). Reduction in ISI scores during treatment correlated with lower return-to-use rates (p-value = .015). Post-treatment episode, ISI scores indicative of insomnia were associated with return to use (p-values < .001) and non-fatal overdose (p-values < .004) at months one, three, and six.

Conclusions

These findings underscore the significant role of insomnia in return to opioid use following OUD treatment, highlighting the importance of addressing sleep disturbances early in OUD treatment. This study also suggests that maintaining sleep health during and after treatment could improve the long-term prognosis for OUD. Interventions targeting insomnia are a promising avenue to improve OUD treatment outcomes.
Systematic review: differences in complete blood count component rhythms
Authors: Busza Anna , Sharma Vani , Ferguson Kendall , Fawcett Andrea , Knoll Justin , Iwanaszko Marta , Zee Phyllis , Fishbein Anna
Published: December 2024

Study Objectives

The complete blood count (CBC) is one of the most commonly ordered blood tests with a large range of reference values that does not consider time of day for interpretation. Our objective was to systematically review this topic to report on peak and trough timing of CBC values.

Methods

A systematic search was performed for studies evaluating any component of the CBC with at least three collections over 24 hours. The studies were screened based on the predetermined eligibility criteria. Meta-analysis of aggregated data was analyzed with polynomial functions and forest plots.

Results

In total, 164 full-text articles were screened and 32 included in the final analysis with 548 total patients considering either leukocytes (n = 13), erythrocytes (n = 7), hemoglobin (n = 5), hematocrit (n = 5), platelets (n = 12), neutrophils (n = 11), lymphocytes (n = 13), monocytes (n = 8), eosinophils (n = 15), or basophils (n = 9). CBC components were analyzed by polynomial and forest plot analysis. Lymphocytes fitted best to a third-degree polynomial function (p = .010) with peak at 2264.87 cells/µL at 23:54 (CI: 1783.44 to 2746.31) with a trough of 1598.91 cells/µL at 10:47 (CI: 1230.12 to 1967.71). Lymphocytes and eosinophils peaked overnight, while erythrocytes, hemoglobin, and hematocrit peaked in the morning, and platelets, neutrophils, monocytes, and basophils peaked in late afternoon. Limitations include small sample size and significant study heterogeneity.

Conclusion

We identified a limited scope of studies characterizing CBC component rhythms. However, we still noted significant differences, particularly with lymphocytes. Future work should evaluate larger datasets to inform time-dependent interpretation of the CBC as we move toward precision medicine.
Soil microbial strategies for climate mitigation—report from a climate action workshop in Las Vegas, Nevada, February 2024
Authors: Beattie Gwyn A , Cotrufo Francesca M , Crowther Thomas W , Edlund Anna , Salles Joana Falcão , Gilbert Jack A , Jansson Janet K , Jensen Paul R , Lennon Jay T , Makhalanyane Thulani , Martiny Jennifer B H , Newman Dianne K , Stevenson Mark
Published: December 2024

Life on Earth faces an existential crisis due to the enduring repercussions of unsustainable human activities since the beginning of the Industrial Revolution. Among the most pressing issues are greenhouse gas emissions, primarily from fossil fuel combustion, unsustainable agricultural practices, as well as the global erosion of the world’s topsoil. While agrochemicals have temporarily increased land productivity, their frequent use has adversely impacted the environment and microbial biodiversity. With half of the global soils already degraded by erosion and a projected 90% at risk by 2050, humanity faces a critical crisis that threatens food production, soil carbon storage, and availability of clean water. In this precarious scenario, microbes and plants may provide promising allies for sustaining life on Earth. Thus, it is crucial for policymakers, scientists, NGOs, and the public to recognize the fundamental importance of the soil microbiome. In February 2024, the workshop “Soil Microbial Strategies for Climate Mitigation” gathered world-leading experts from the most relevant research fields, as well as industry innovators, communicators, artists, and policymakers, to propose soil microbiome-based interventions aimed at enhancing carbon dioxide (CO2) drawdown and mitigating soil erosion. The workshop focused on innovative soil microbial inoculant approaches, examining methodologies for measuring soil carbon, enhancing plant health and soil structure, proposing an action plan, and forming collaborative strategies.