bluuebunny/crossref_metadata_2025 huggingface dataset:
(055) HEAVY METAL EXPOSURE AND ERECTILE DYSFUNCTION: INSIGHTS FROM THE ALL OF US RESEARCH PROGRAM
Authors: Ryan J , Angulo-Llanos L , Yu H , Punnen S , Masterson T
Published: December 2024

Introduction

Erectile dysfunction (ED) has long been associated with cardiovascular disease, a sedentary lifestyle, smoking, obesity, and diabetes. However, the role of environmental factors in ED is still not fully understood. Current literature is unclear on the relationship between heavy metal exposure and ED, despite growing evidence that such exposure can lead to oxidative stress, thereby increasing the risk of various diseases. The All of Us (AoU) Research Program is a prospective clinico-genomic database that focuses on individuals from underrepresented populations.

Objective

We aimed to use the AoU database to examine how high levels of heavy metals in the blood relate to erectile dysfunction.

Methods

AoU release version 7 was analyzed. Men with an EHR-coded diagnosis of ED were included in the analysis. Serum and blood levels of lead, selenium, magnesium, zinc, and copper were analyzed. Patients with elevated heavy metal levels in the blood were defined as those with lead levels above 25 μg/dL, selenium levels above 160 μg/L or 0.1 ppm, magnesium levels above 2.2 mg/dL, zinc levels above 120 μg/dL, and copper levels above 140 μg/dL or ceruloplasmin levels above 40 mg/dL. P-values were calculated using univariate logistic regression and chi-squared tests with Bonferroni correction.

Results

The total cohort of men was 153 582, with 15 523 of them having ED (10.1%). Of these men, 19.2% were Black, 62.9% were White, and 17.9% were of another race. Among men with ED, 66.1% were over 65 years old, 26.8% were 45-64 years old, and 4.4% were 18-44 years old. Patients with elevated lead (OR: 4.58, p < 0.001), zinc (OR: 2.07, p = 0.005), or magnesium (OR: 1.39, p < 0.001) levels were more likely to have ED. However, elevated copper (OR: 0.67, p = 0.005) and selenium (OR: 0.955, p = 0.874) levels were not associated with a higher rate of ED. Overall, men with ED who had elevated heavy metal levels were more likely to have a higher BMI (p = 0.010), be unemployed (p < 0.001), have low income (p < 0.001), rent their homes (p < 0.001), and be older (p < 0.001). There was no significant difference in education status (p = 0.172) or race (p = 0.117).

Conclusions

Using a large prospective database that focuses on underserved populations, our study found that heavy metal levels higher than established cutoffs were associated with higher rates of ED. Lead appeared to have the largest effect on ED rates, while zinc surprisingly had a higher odds ratio of being elevated in patients with ED. These results add to the relatively scant literature on heavy metals' influence on ED. Lastly, our findings suggest that it is important to include heavy metals in the risk assessment for ED.

Disclosure

No.
(118) SURGICAL OUTCOMES OF BENIGN SCROTAL SURGERY PERFORMED UNDER LOCAL ANESTHESIA
Authors: Ko Y , Fidel M , Shah J , Roque C , Patel P
Published: December 2024

Introduction

General and spinal anesthesia are often used to perform benign scrotal surgery. However, these methods yield substantial healthcare costs, potential side effects, and given the benign nature of the conditions, patients often face considerable wait times to receive surgical care. The use of local anesthesia (LA) only has previously been shown to demonstrate satisfactory patient tolerability for scrotal surgery. However, evidence is limited, and further research is required to evaluate its safety.

Objective

We sought to evaluate patient intolerability, intra-operative complications and 4–6-week procedure-related adverse events.

Methods

We conducted a retrospective study of patients undergoing the following procedures, 1) hydrocelectomy, 2) spermatocelectomy, and 3) epididymectomy, at a Canadian ambulatory surgical centre from October 2022 to June 2024. LA administration was performed through a spermatic cord block as well as along the median raphe for all procedures. Procedures performed for a large hydrocele or spermatocele where an early block was not possible, were subsequently performed after delivery of the testicle. Baseline characteristics, intra-operative events, and post-operative adverse events were collected.

Results

From October 2022 to June 2024, a total of 72 procedures were performed. Of these procedures, 39% (n = 28) were hydrocelectomies, 33% (n = 24) were spermatocelectomies, and 28% (n = 20) were epididymectomies. The mean patient age was 52.6 ± 14.3 years with a BMI of 31.2 ± 11.1. No procedures were aborted due to patient intolerability nor were there any reported intra-operative complications. At 4-6 weeks post-operative follow-up, no patients sought care from their family doctor with only 1.4% (n = 1) patients requiring an emergency department visit for a wound infection. No patients required hospital admission.

Conclusions

Our early findings demonstrate the safety and feasibility of performing surgical scrotal procedures in an outpatient setting under LA. Safely performing these procedures in an outpatient setting can reduce patient wait times for scrotal surgeries, boost tertiary care centre efficiency, and optimize the use of scarce resources such as operating rooms and inpatient facilities. Further longer-term follow-up is needed to evaluate recurrence rates.

Disclosure

Any of the authors act as a consultant, employee or shareholder of an industry for: Boston Scientific.
(119) THE COST OF CLOMIPHENE FOR MALE INFERTILITY TREATMENT: REGIONAL PRICE VARIABILITY ACROSS THE UNITED STATES
Authors: Manafi E , Furtado T , Loeb C , Eleswarapu S , Mills J , Andino J
Published: December 2024

Introduction

Clomiphene, known by the brand-name Clomid, is used off-label as empiric medical therapy to improve testosterone and sperm parameters in men. Despite its role in the medical management of male infertility and hypogonadism, this selective estrogen receptor modulator (SERM) is rarely covered by insurance for these indications. Typically taken daily or every other day for 3-6 months, this lack of coverage makes the high and variable prices a barrier to fertility care for many patients.

Objective

This study sought to analyze the price variability of compounded clomiphene and brand name Clomid across the United States and identify regions where patients might face potential undue financial burden based on their geographical location.

Methods

Prices for compounded clomiphene 25 mg-50 mg and brand-name Clomid (50 mg) for 30-day and 90-day supplies were collected from 136 compounding pharmacies nationwide via phone; national retail pharmacy prices were recorded via GoodRx. The weighted average price per pill, minimum, and maximum values for each dosage were calculated. States were categorized into four regions (Northeast, Midwest, West, South) for regional analysis.

Results

The weighted mean price per pill for clomiphene 25 mg, clomiphene 50 mg, and Clomid were $2.21 ± 1.24; $2.60 ± 1.49; and $8.41 ± 1.53, respectively, from compounding pharmacies. In comparison, the national Clomid retail pharmacy average with GoodRx discount was $4.30 ± 0.29. The weighted per-pill averages in each region are presented in Table 1. Compounded clomiphene is a significantly more affordable alternative to the brand-name Clomid given the limited insurance coverage (p < 0.001). Additionally, patients face significantly varying average prices across different regions (p = 0.0441), with particularly higher average prices in the West and Northeast. The least and most expensive prices per pill of brand-name Clomid (without GoodRx) were $7.51 and $10.83 in the Northeast, $4.50 and $13.21 in the Midwest, $6.34 and $11.67 in the South, and $5.16 and $13.44 in the West. The greatest variation was in the Midwest, at $8.71 per pill ($784 for 90 pills). This was followed by the West with a difference of $8.28, the South with $5.33, and the Northeast with $3.32 (Fig. 1).

Conclusions

There are significant differences in the pricing of clomiphene (Clomid) across regions, with some regions experiencing more notable internal variations. These pricing trends could potentially hinder access to treatment and pose substantial obstacles for patients.

Disclosure

No.
(122) HUMAN FACTORS AFFECTING RECOVERY OF SPERM MOTILITY AFTER CRYOPRESERVATION: A RETROSPECTIVE ANALYSIS
Authors: Li M , Fan A , Hsieh T
Published: December 2024

Introduction

Although studies have suggested that sperm motility may play a role in predicting the success of assisted reproductive technology, current studies on factors affecting recovery of sperm motility after cryopreservation are largely limited to evaluating cryopreservation techniques.

Objective

We sought to evaluate human factors that affect the recovery of sperm motility after cryopreservation.

Methods

We conducted a retrospective analysis of all patients who underwent sperm cryopreservation at our institution from September 2021 through January 2024. We measured pre- and post-thaw motility, and collected demographics, medical and surgical history, and pre-retrieval laboratory values from the electronic medical record. Student’s t-tests were used to compare continuous variables, and Pearson’s chi-squared tests were used for categorical variables. All analyses were conducted in R version 4.4.0, and p < 0.05 was considered statistically significant.

Results

A total of 184 patients underwent sperm cryopreservation. Among the cohort, the mean age was 30.4 (SD 9.07) with a mean BMI of 25.9 (SD 4.87). The mean sperm motility prior to freezing, after freezing, and percent recovery was 45.5% (SD 22.1), 23.7% (SD 13.8), and 53.9% (SD 24.5), respectively. Of the factors analyzed, increased age was associated with decrease sperm motility percent recovery (p = 0.005). Hormonal evaluation of the cohort showed 57 patients had luteinizing hormone values collected pre-retrieval, which was positively correlated with sperm motility recovery (p = 0.054). Estradiol, testosterone, prolactin, and follicle-stimulating hormone levels also did not significantly correlate with sperm motility recovery. Race, BMI, history of diabetes mellitus, alcohol use, tobacco use, cancer history, radiation or chemotherapy history, history of hypogonadism, or history of prior children did not affect sperm motility recovery.

Conclusions

Our findings suggest that age is negatively correlated with recovery of sperm motility. These results may help guide physicians counseling patients if additional samples should be submitted for cryopreservation.

Disclosure

No.
An examination of sexual function & distress among sexual minority & heterosexual women seeking care at menopause and sexual health specialty clinics
Authors: Sobel Talia , Faubion Stephanie S , Vencill Jennifer A , Cole Kristin , Winham Stacey , Williams Courtney , Kling Juliana M
Published: December 2024

Background

Sexual minority women (SMW) have worse mental and physical health outcomes compared to heterosexual women, but literature on sexual function in SMW compared to heterosexual women is lacking.

Aim

To evaluate sexual function and sexual distress in women across sexual orientations.

Method

Questionnaire data were analyzed for women aged 18 and older who presented to women’s health clinics at Mayo Clinic in Minnesota, Arizona, and Florida from 2016 to 2023. Female Sexual Function Index (FSFI) and Female Sexual Distress Scale–Revised (FSDS-R) scores assessed sexual dysfunction (FSFI ≤ 26.55 and FSDS-R ≥ 11). Multivariable logistic models adjusted for confounding factors.

Outcomes

Our main outcome was female sexual dysfunction as defined by a composite of FSFI ≤ 26.55 and FSDS-R ≥ 11 to include both sexual function and sexual distress.

Results

Of 6241 sexually active women, 3% were SMW and 97% were heterosexual women. The majority were White (93%), with average age 51.6 years old. There was no significant difference in sexual dysfunction rates between heterosexual and SMW by combined endpoint on univariate or multivariable analysis. SMW had higher total FSDS scores (17 vs 15, P = 0.037), indicating more sexual distress.

Clinical Implications

Sexual health concerns may differ between SMW and heterosexual women emphasizing the need for inclusive, culturally competent care.

Strengths & Limitations

This study assessed the association of sexual orientation and sexual dysfunction by incorporating sexual functioning problems and sexual distress. Limitations include a small number of SMW and a predominantly White, married, employed, and educated study sample, limiting the generalizability of the findings.

Conclusion

Rates of sexual dysfunction were similar between mostly White SMW and heterosexual women presenting to tertiary care centers. SMW reported more sexual distress than heterosexual women. Evaluating these variables in larger, more diverse cohorts is a critical next step.
Mapping of functional erectogenic nerves on the rat prostate
Authors: Unal Selman , Mi Ruifa , Musicki Biljana , Hoke Ahmet , Burnett Arthur L
Published: December 2024

Background

Preservation of erectogenic nerves during radical prostatectomy (RP) is hampered by limited understanding of their precise localization, due to their complex, intertwined paths, and the inherent individual variations across patients. Because erection utilizes a subset of cavernous nerves (CNs) that in response to sexual stimuli reveal phosphorylation of neuronal nitric oxide synthase (nNOS) on its stimulatory site Ser-1412, we hypothesized that delineation of nerves containing phosphorylated (P)-nNOS on Ser-1412 would establish the location of functional erectogenic nerves within the periprostatic region.

Aim

To identify the distribution and quantity of functional erection-relevant ([P-nNOS]-containing) nerves in the periprostatic area and discriminate them among the CNs distribution. We further evaluated whether functional communication exists between contralateral CNs.

Methods

Young adult male Sprague–Dawley rats underwent electrical stimulation of the CNs to induce penile erection via phosphorylation of nNOS on Ser-1412 (6 V for 2 min, n = 6). No stimulation group served as control (n = 6). The prostate and adjacent structures were collected and processed for whole-mount double-staining with TuJ1 antibody (a pan-axonal marker) and P-nNOS (n = 3 for stimulation, n = 3 for no stimulation), or total nNOS and P-nNOS (n = 3 for stimulation, n = 3 for no stimulation), followed by modified optical clearing and microscopic examination. Nerve quantification was done by systematic counting.

Outcomes

Location and quantification of functional erectogenic nerves.

Results

In the male rat, we obtained a map of P-nNOS-containing nerves in the periprostatic area, which are relevant for penile erection. Only 17.5% of all nerves, and only 28.4% of the total nNOS-containing nerves in the periprostatic region are functionally erectogenic nerves. Furthermore, there is no functional innervation between contralateral (stimulated and non-stimulated) CNs.

Clinical Implications

This basic science study is expected to provide a foundation for subsequent studies at the human level. Understanding the erection-relevant nerve distribution in the periprostatic area is expected to advance nerve-sparing RP at the human level to improve sexual function outcomes.

Strengths and Limitations

This is the first study to describe and quantitate a subset of functional erection-relevant (P-nNOS-containing) nerves in the periprostatic area. Our study differs from previous studies where nerves containing total nNOS were localized without specifying which nerves produce erection. However, because this study comprised a relatively small number of rats, further studies with a bigger sample size or other model animals are warranted.

Conclusion

Only a subset of nerve fibers in the periprostatic region represent functional erectogenic nerves, characterized by the expression of P-nNOS (Ser-1412).
Phloem: a missing link in understanding tree growth response in a changing environment
Authors: Gričar Jožica
Published: December 2024

This article comments on:

Dusart N, Moulia B, Saudreau M, Serre C, Charrier G, Hartmann FP. 2024. Differential warming at crown scale impacts walnut primary growth onset and secondary growth rate. Journal of Experimental Botany 75, https://doi.org/10.1093/jxb/erae360
Overcoming weeds: breeding herbicide-resistant crops via directed evolution
Authors: Ma Liang , Guo Yan
Published: December 2024

This article comments on:

Qian H, Shi H. 2024. Herbicide-resistant 4-hydroxyphenylpyruvate dioxygenase variants identified via directed evolution. Journal of Experimental Botany 75, https://doi.org/10.1093/jxb/erae330
Set-Off Between Solvent Parties: Common Law
Authors: Derham Rory
Published: December 2024

This chapter tackles the notion of set-off between solvent parties under common law. Before the establishment of the first Statute of Set-off in 1729, there was no general right of set-off available to a defendant in a common law action when he or she was being sued by a solvent plaintiff. Before the Judicature Acts, the courts applied the principle that a set-off under the Statutes could only be pleaded in bar to the plaintiff’s action if the set-off was available at the commencement of the action. The chapter cites that set-off under the Statutes is commonly described as a procedural defence. It also discusses the general principles of common law abatement.
Practical and statistical aspects of subgroup analyses in surgical neuro-oncology: A comprehensive review from the PIONEER consortium
Authors: Gerritsen Jasper K W , Karschnia Philipp , Young Jacob S , van den Bent Martin J , Chang Susan M , Smith Timothy R , Nahed Brian V , Rincon-Torroella Jordina , Bettegowda Chetan , Sanai Nader , Krieg Sandro M , Maruyama Takashi , Schucht Philippe , Broekman Marike L D , Tonn Joerg-Christian , Wen Patrick Y , De Vleeschouwer Steven , Vincent Arnaud J P E , Hervey-Jumper Shawn , Berger Mitchel S , Mekary Rania A , Molinaro Annette M
Published: December 2024

Subgroup analyses are essential to generate new hypotheses or to estimate treatment effects in clinically meaningful subgroups of patients. They play an important role in taking the next step toward personalized surgical treatment for brain tumor patients. However, subgroup analyses must be used with consideration and care because they have significant potential risks. Although some recommendations are available on the pearls and pitfalls of these analyses, a comprehensive guide is lacking, especially one focused on surgical neuro-oncology patients. This paper, therefore, reviews and summarizes for the first time comprehensively the practical and statistical considerations that are critical to this field. First, we evaluate the considerations when choosing a study design for surgical neuro-oncology studies and examine those unique to this field. Second, we give an overview of the relevant aspects to interpret subgroup analyses adequately. Third, we discuss the practical and statistical elements necessary to appropriately design and use subgroup analyses. The paper aims to provide an in-depth and complete guide to better understand risk modeling and assist the reader with practical examples of designing, using, and interpreting subgroup analyses.
Designing a time-dependent therapeutic strategy using CDK4/6 inhibitors in an intracranial ATRT model
Authors: Martin Brice , Guadix Sergio W , Sathian Rekha , Laramee Madeline , Pandey Abhinav , Ray Ishani , Wang Amy , Davuluri Ramana , Thomas Craig J , Dahmane Nadia , Souweidane Mark
Published: December 2024

Background

Inhibitors targeting cyclin-dependent kinases 4 and 6 (CDK4/6), crucial for cell cycle regulation, have shown promise in early-stage studies for treating central nervous system (CNS) tumors. However, challenges such as limited CNS penetration, optimal treatment duration, and systemic side effects have impeded their clinical translation for pediatric brain tumors (PBTs).

Methods

We evaluated the potency of CDK4/6 inhibitors across various PBT cell lines, focusing particularly on palbociclib against atypical teratoid rhabdoid tumor (ATRT) with cell viability assays and gene expression analysis. Additionally, we assessed the efficacy and safety of intrathecal (IT) delivery of palbociclib through neurotoxicity and pharmacokinetic studies, along with survival assessments in murine leptomeningeal ATRT models.

Results

Palbociclib showed the highest potency across various PBT cells, with extended treatments reducing growth inhibition 50 (GI50) values from the micromolar to nanomolar range. It suppressed critical cell cycle genes (CCNB1, CCNA2, CDK1) in BT16 ATRT cells. Neurotoxicity (GFAP, CD45, NeuN, Iba1) and pharmacokinetic assays confirmed IT route as a feasible and effective method for delivering palbociclib to the cerebrospinal fluid (CSF), avoiding systemic toxicity and enhancing drug concentration to the brain. Finally, metronomic IT delivery using an osmotic pump (OP, 48 mg/kg) increased survival in 2 murine leptomeningeal ATRT models, showcasing its potential as a novel therapy for leptomeningeal tumors.

Conclusions

Metronomic IT delivery of palbociclib enhances drug efficacy and safety, improves survival, and offers a promising treatment strategy for PBTs with CSF dissemination.
Rice Bran Extraction and Stabilization Methods for Nutrient and Phytochemical Biofortification, Nutraceutical Development, and Dietary Supplementation
Authors: Das Prajna Priyadarshini , Gul Mir Zahoor , Weber Annika M , Srivastava Rakesh K , Marathi Balram , Ryan Elizabeth P , Ghazi Irfan A
Published: December 2024

Rice is a global staple food crop for nearly half of the world's population. Rice bran along with the germ are essential components of whole-grain rice and have immense potential for enhancing human nutrition. Rice bran has a unique composition and distinct requirements for processing before it can be consumed by humans when compared with other cereal brans. The comprehensive overview and synthesis of rice bran processing include extending the shelf life for functional food product development and extraction of bioactive components. This narrative review highlights established and innovative stabilization approaches, including solvent extraction and enzymatic treatments, which are critical methods and technologies for wider rice bran availability. The nutrient and phytochemical profiles of rice bran may improve with new cultivar development and food-fortification strategies. The postharvest agricultural practices and processing techniques can reduce food waste while also supporting growers to produce novel pigmented cultivars that can enhance nutritional value for human health.
London Major Trauma System: a review of an organised trauma system and the challenges it faces
Authors: Edmunds Matthew
Published: December 2024

London Major Trauma System (LMTS) was the first organised trauma system in the United Kingdom. It was created in 2010 in response to multiple reviews that suggested a large number of deaths from trauma may have been preventable.

LMTS has all the features of a modern organised trauma system, including regionalisation, integration of care, transfer services, trauma teams, and a world leading research service. Since its introduction the benefits on mortality, morbidity, and other key metrics have been widely demonstrated. Despite its success, LMTS still faces a number of challenges; most notably from the ageing population, but also in ensuring equity of improvements across the entirety of the trauma network and throughout the whole patient journey. The very nature of LMTS being an inclusive and organised trauma system will help it in facing these challenges.
What should you have in your little black bag? A letter to a young doctor
Authors: Schattner Ami
Published: December 2024

Rather than looking at which instruments to put in the traditional physician’s black bag, the changing face of medicine suggests that some virtual assets assume prime importance. With a solid background of core knowledge and skills acquired through medical school but continuously developed and updated, several habitual attitudes are advocated—each aiming to address a different facet of concerns in today’s time-constrained, often impersonal, fast-changing, information-overloaded, and highly technological practice. They include humility, curiosity, “red flag” identification, and reflexive database consultation—each with myriad, diverse advantages.
On the Family Origins of Human Capital Formation: Evidence from Donor Children
Authors: Lundborg Petter , Plug Erik , Rasmussen Astrid Würtz
Published: December 2024

We introduce a novel strategy to study the intergenerational transmission of human capital skills, net of genetic skill transfers. For this purpose, we use unique Danish data on children conceived through sperm and egg donation in in vitro fertilization treatments to estimate the relationship between child test scores and parental years of schooling. Because the assignment of donors is not selective, these parental schooling estimates allow for a causal nurture interpretation. Once we take account of genes, we find that only the education of mothers matters: the association between father’s education and child test scores (in reading and math) is insignificant and practically zero, whereas the association between mother’s education and child test scores (in reading, not in math) is significant and large, and as large as the association we estimate for mothers of non-donor children.
A multivariable prediction model to identify anti-CCP positive people in those with non-specific musculoskeletal symptoms in primary care
Authors: Siddle Heidi J , Wilson Michelle , Nam Jacqueline L , Garcia-Montoya Leticia , Duquenne Laurence , Mankia Kulveer , Emery Paul , Hensor Elizabeth M A
Published: December 2024

Objectives

We aimed to develop a prediction model identifying people presenting to primary care with musculoskeletal symptoms likely to be anti-CCP positive and therefore at risk of developing RA.

Methods

Participants aged ≥16 years, with new-onset non-specific musculoskeletal symptoms and no history of clinical synovitis, completed a symptom questionnaire and had an anti-CCP test. Model development used LASSO-penalized logistic regression, performance was assessed using area under the receiver operating characteristic curve (AUROC) and decision curve analysis, model over-fit was estimated using bootstrapping and cross-validation. Participants were followed-up at 12 months for RA or seronegative/undifferentiated inflammatory arthritis diagnosis.

Results

Analysis included 6879 participants; 203 (2.95%) of whom were anti-CCP positive. Eleven predictors were retained: male sex, first-degree relative with RA, ever smoked and joint pain in: back, neck, shoulders, wrists, hands/fingers, thumbs, knees, feet/toes. AUROC was 0.65 (95% CI 0.61, 0.69, optimism = 0.03). Using a 4% decision threshold, the model recommended an anti-CCP test in 1288 (18.7%) participants, 78 (6.1%) of whom were anti-CCP positive, compared with 125/5591 (2.2%) below the threshold. Net benefit was 0.0040 (0.0020 corrected). Forty-eight participants were diagnosed with inflammatory arthritis/RA within 12 months. Of those who were above the threshold and anti-CCP positive, 32.1% developed inflammatory arthritis/RA compared with 0.4% of those who were anti-CCP negative. Of those below the threshold, 0.3% were diagnosed with inflammatory arthritis/RA.

Conclusions

Targeted anti-CCP testing in primary care may aid earlier identification of people at risk of RA, prompting specialist referral to rheumatology for earlier diagnosis and initiation of disease-modifying therapy.
Novel photopeak-independent correction method for internal activity calculation of 99mTc: a simulation study
Authors: Mercado-Quintero Alfredo V , Torres-García Eugenio , Isaac-Olivé Keila , Torres-García Rocío , Aranda-Lara Liliana , Torres-Velázquez Hansel
Published: December 2024

This paper presents a new method for correcting the contribution of scattered radiation to the measurement of 99mTc internal activity in nuclear medicine patients using gamma cameras. So, this study aims to derive scattering correction factors by Monte Carlo simulation for anterior and posterior count rates (${I}_{\mathrm{A}}$ and ${I}_{\mathrm{P}}$) in the conjugate view method, enabling more precise estimation of activity A(t) compared to traditional trapezoidal and triangular approximations. The new approach eliminates the need to use photopeak for determining the fraction of scattered photons. Our results showed differences of <3% with respect to the real activity and 11% for the trapezoidal and triangular approaches.
Advances in MRI Research for First-Episode Schizophrenia: A Selective Review and NSFC-Funded Analysis
Authors: Yang Qi , Pan Xingchen , Yang Jun , Wang Ying , Tang Tingting , Guo Weisheng , Sun Ning
Published: December 2024

Background and Hypotheses

The causes of schizophrenia remain unclear, and research has been hindered by the lack of quantifiable standards. However, magnetic resonance imaging (MRI) is addressing these challenges, revealing critical neurobiological details and emphasizing its importance in both evaluation and treatment.

Study Design

First, we reviewed the progress of research on structural MRI (sMRI), functional MRI (fMRI), multimodal/multiomics analysis, artificial intelligence, and neuromodulation in first-episode schizophrenia (FES) over the past 5 years. Second, we summarize the current state of schizophrenia research funded by the National Natural Science Foundation of China (NSFC) to facilitate academic exchange and cooperation both domestically and internationally.

Study Results

sMRI has identified early neurodevelopmental biomarkers in FES patients, and fMRI has highlighted functional abnormalities across disease stages. Multimodal/multiomics analysis has revealed complex brain–neurobiology interactions. Neuromodulation techniques, which directly modulate neural activity in specific brain regions, offer promising long-term benefits for stabilizing conditions and enhancing patients’ quality of life. NSFC-funded analysis shows China is increasing its funding for schizophrenia research, though funding distribution remains uneven. The research focus has shifted from a single perspective on brain structure and function to multichannel, multimodal comprehensive analysis methods. This progress has driven the integration of machine learning-driven multiomics research, aiming to construct disease classification models, explore disease mechanisms, and guide treatment from multidimensional and interdisciplinary perspectives.

Conclusions

MRI technology has provided new perspectives for the diagnosis and treatment of schizophrenia, especially the neurobiological foundations of the disease. Support from the NSFC provides a scientific and financial basis for future research and treatment, heralding scientific discoveries and technological innovations in this field and bringing hope to schizophrenia patients.
Metformin for the Prevention of Antipsychotic-Induced Weight Gain: Guideline Development and Consensus Validation
Authors: Carolan Aoife , Hynes-Ryan Caroline , Agarwal Sri Mahavir , Bourke Rita , Cullen Walter , Gaughran Fiona , Hahn Margaret K , Krivoy Amir , Lally John , Leucht Stefan , Lyne John , McCutcheon Robert A , Norton Michael J , O’Connor Karen , Perry Benjamin I , Pillinger Toby , Shiers David , Siskind Dan , Thompson Andrew , O’Shea Donal , Keating Dolores , O’Donoghue Brian
Published: December 2024

Background

Overweight and obesity are highly prevalent in people with severe mental illness (SMI). Antipsychotic-induced weight gain (AIWG) is one of the most commonly reported and distressing side effects of treatment and people living with SMI place a high value on the avoidance of this side effect. Metformin is the most effective pharmacological intervention studied for the prevention of AIWG yet clear guidelines are lacking and evidence has not translated into practice. The aim of this research was to develop a guideline for the use of metformin for the prevention of AIWG.

Study Design

The appraisal of guidelines for research and evaluation II instrument (AGREE II) was followed for guideline development. Literature was reviewed to address key health questions. The certainty of evidence was evaluated using GRADE methodology and an evidence-to-decision framework informed the strength of the recommendations. A consensus meeting was held where the algorithm and strength of recommendations were agreed. An independent external review was conducted involving experts in the field, including patient and public partners.

Study Results

Metformin is the only pharmacological agent that has demonstrated efficacy for preventing AIWG. Co-commencement with antipsychotic medicines can reduce the extent of weight gain by 4.03 kg (95% CI −5.78 kg to −2.28 kg) compared to controls. A guideline for the use of metformin for the prevention of AIWG was developed with specific recommendations for co-commencement of metformin at initiation with an antipsychotic or commencement if certain criteria are present. Core recommendations were graded as strong by consensus agreement.

Conclusions

This is the first published evidence-based guideline using the AGREE II framework and GRADE methods for the use of metformin to prevent AIWG incorporating recommendations for co-commencement. Implementation and evaluation of the guideline will be supported by a shared decision-making package and assessment of barriers and facilitators to implementation.
Rentiership and intellectual monopoly in contemporary capitalism: conceptual challenges and empirical possibilities
Authors: Baines Joseph , Hager Sandy Brian
Published: December 2024

In recent years, the concepts of rentiership and intellectual monopoly have gained prominence in discussions about the weakening link between corporate profitability and capital investment in high income countries. However, there have been few if any attempts to construct measures for rentiership and intellectual monopoly using firm-level financial data. The absence of such work, we argue, is symptomatic of challenges in delineating what qualifies as rent—whether it be intangible rent or otherwise. In place of static conceptions of rent and intellectual monopoly, we develop a framework for analyzing rentierization and intellectual monopolization as dynamic and variegated processes that are closely related to financialization. We apply the framework to the analysis of the transformation of non-financial firms in the USA since the mid-twentieth century and show how it helps clarify the linkages between firm-level dynamics and trends associated with household inequality, corporate stratification and secular stagnation.
Comparison of clinical and laboratory data between hantavirus infection and leptospirosis: a retrospective case series study in southern Taiwan
Authors: Lo Shih-Hao , Chen Tun-Chieh , Lin Chun-Yu , Hsieh Hsiao-Chen , Lai Ping-Chang , Lien Wei-Li , Yeh Yen-Cheng , Lee Ing-Kit , Chen Yen-Hsu , Lu Po-Liang , Chang Ko
Published: December 2024

Background

Leptospirosis (LS) and hantavirus (HV) are rodent-borne diseases and share similar clinical manifestations, posing diagnostic challenges.

Methods

This retrospective study compared clinical characteristics, laboratory data, complications and outcomes of 33 LS and nine HV cases in Kaohsiung, Taiwan, from 2006 to 2021.

Results

Both LS and HV diseases had high rates of acute kidney injury (84.8% vs 66.7%) and hepatitis (65.6% vs 88.9%); LS showed more hyperbilirubinemia (70% vs 12.5% in HV, p=0.005), higher initial creatinine levels (2.9 vs 1.37, p=0.018) and elevated initial C-reactive protein (218.3 vs 28.6 mg/dl, p<0.001), but lower initial lymphocyte percentage (6.63% vs 14.2%, p=0.005) and platelets (138.7/mm3 vs 68.9, p=0.016) compared with HV. Microscopic hematuria was significantly more prevalent in LS (80% vs 28.65% in HV, p=0.016). Notably, the LS and HV groups exhibited statistically significant differences in thrombocytopenia (57.5% vs 100%, p=0.019), hyperbilirubinemia (70% vs 12.5%, p=0.005), shock (45.5% vs 0%, p=0.016) and hematuria (80% vs 28.6%, p=0.016). Neither group experienced fatalities.

Conclusions

Fever, thrombocytopenia and acute kidney injury alert physicians to consider LS and HV for differential diagnosis. Elevated bilirubin, along with hematuria or shock, suggests a preferred diagnosis for LS.
Multi‐omics analysis reveals alterations of breastmilk metabolites and proteins in Hong Kong lactating mothers
Authors: Jiang Lilong , Yeung Oi‐Yee , Ho Wing‐Wa , Shum Tim‐Fat , Wong Man‐Sau , Lam Carly S. Y. , Chiou Jiachi
Published: December 2024

The nutritional contents of breastmilk (BM) directly participate in neonatal metabolism via breastfeeding. Currently, there is limited research on BM metabolites and proteins compositions, and their alterations during the long lactation period in Hong Kong mothers. In this study, liquid chromatography–mass spectrometry‐based metabolomics, lipidomics and proteomics studies were applied to compare the compositions in BM of Hong Kong lactating mothers at the 2nd, 6th, and 12th months after delivery. Distinct metabolomics and lipidomics signatures in 6th month versus 2nd month and 12th month versus 2nd month were observed, and a total of 19 differential metabolites and 105 lipids were identified. Metabolomics study showed the significant alterations in key pathways involved in biotin metabolism, amino acid, and fatty acid‐associated metabolisms. Lipidomics analysis indicated the accumulation of triglyceride and ceramide during the lactation period. The remodeling of glycerophospholipids was also observed during 12‐month period. Moreover, 28 differentially expressed proteins were identified and mainly associated with GO functions and KEGG pathways of ribosome and complement and coagulation cascades, which were validated by network analysis. Our research contributes to the understanding of the BM compositions and differences during the long lactation period in postpartum women of Hong Kong.
Visualized Pattern-Based Hypothesis Testing on Exhaustion, Resilience, Sleep Quality, and Sleep Hygiene in Middle-Aged Women Transitioning Into Menopause or Postmenopause
Authors: Jeon Mi Yang , Lee Seonah
Published: December 2024

Exploratory data analysis involves observing data in graphical formats before making any assumptions. If interesting relationships or patterns among variables are identified, hypotheses are developed for further testing. This study aimed to identify significant differences in the levels of exhaustion, resilience, sleep quality, and sleep hygiene according to the personal characteristics of middle-aged women transitioning into menopause or postmenopause through exploratory data analysis. A total of 200 women aged 44 to 55 years were recruited online in August 2023. Data were collected using valid instruments and analyzed through data visualization, pattern identification in the visualized data, and hypothesis establishment based on the visualized patterns. Hypotheses were tested through the independent-samples t test, analysis of variance, and the Kruskal-Wallis test. A total of 11 patterns and corresponding hypotheses were identified. According to the statistically supported pattern-based hypotheses, middle-aged women who were in their perimenopausal period perceived themselves as unhealthy, had professional occupations, and had the highest level of exhaustion and the lowest levels of resilience, sleep quality, and sleep hygiene. This study demonstrated that data visualization is an efficient way to explore relationships or patterns between data. Data visualization should be considered an informatics solution that can provide insight in the field of healthcare.
Iatrogenic Erosion of Orbital Walls due to Expanding Hydrogel Explant
Authors: Ang Terence , Quigley Clare , Slattery James , Selva Dinesh
Published: December 2024

Hydrogel scleral buckles are a hydrophilic explant that may lead to significant delayed complications. They can insidiously enlarge over decades and may mimic an orbital tumor or cyst. The authors report a case of an expansive hydrogel scleral explant in a previously eviscerated socket. A 58-year-old male presented with a 2-week history of severe pain in his left anophthalmic socket. And 31 years prior, he had sustained OS trauma and undergone a series of surgeries. Details of these procedures were unavailable; however, he had ultimately proceeded to globe evisceration. MRI revealed a large lobulated cyst-like orbital mass with internal calcification, which had expanded the left orbit with erosion of the medial wall, lateral wall, and roof. It extended to involve the ethmoid and frontal paranasal sinuses. He proceeded to a lateral orbitotomy, revealing the lesion to be an expanded hydrogel scleral buckle explant. Postoperatively, there was a significant improvement in his pain.
Systemic Hypothermia in the Acute Management of Traumatic Optic Neuropathy in a Murine Animal Model
Authors: Tse Brian C. , Wang Hua , Dvoriantchikova Galina , Pelaez Daniel , Tse David T.
Published: December 2024

Purpose:

To examine the effects of systemic hypothermia on retinal ganglion cell survival and visual outcomes after optic nerve trauma in a sonication-inducted traumatic optic neuropathy murine animal model.

Methods:

Twenty mice underwent sonication-inducted traumatic optic neuropathy. Afterward, 10 mice were placed on a warming pad set to 36°C, and 10 mice were placed on a table. General anesthesia was maintained for 3 hours with subcutaneous injections of ketamine. The rectal temperature was measured every 15 minutes. Pattern electroretinograms were obtained at 2, 4, and 6 weeks. Mice were sacrificed at 6 weeks, and retinal ganglion cell counts were performed.

Results:

The hypothermia group had an average rectal temperature of 23.1°C; the control group was 33.3°C. At 6 weeks, the hypothermia group had larger a-wave amplitudes (18.19 µV) than the control group (12.75 µV) (p < 0.05). At 6 weeks, retinal ganglion cell density over the entire retina was significantly higher in the hypothermia group versus the control (p < 0.0001).

Conclusions:

The hypothermia treatment group had significantly higher retinal ganglion cell density and pattern electroretinogram a-wave amplitudes 6 weeks after injury than the control group. Systemic hypothermia may have a neuroprotective effect when initiated immediately after sonication-inducted traumatic optic neuropathy.
Cataract Surgery and Intraocular Lens Implantation in Aviation Pilots
Authors: Mendes João , Ribeiro Filomena J
Published: December 2024

The rising age of pilots and the extension of retirement age underscore the importance of investigating Presbyopia correction intraocular lenses during cataract surgery for Aviation Pilots.

This study aims to assess recommendations from aviation regulatory agencies, providing guidance on the use of multifocal intraocular lenses in both commercial and military pilots.

A review analysed the perspectives of aviation regulatory agencies regarding the implantation of multifocal intraocular lenses in pilots. Findings reveal a lack of consensus among agencies regarding the use of multifocal intraocular lenses. Some adopt a permissive stance, permitting their use, while others maintain restrictive approaches. Variations in the post-cataract surgery unfit assessment period were observed, ranging from six to twelve weeks.

The implantation of multifocal intraocular lenses in aviation pilots remains contentious. Further research is crucial to address unresolved aspects associated with using multifocal intraocular lenses in this context.
Proximal Tibia Fractures
Authors: Truong Phong , Bowen Richard E.
Published: December 2024

Proximal tibia fractures in children pose challenges in management due to the complex anatomy in this region. The relationship between the proximal tibial physis, proximal tibial apophysis, extensor mechanism, and nearby vascular structures allows for potential injuries from toddler-aged children through adolescence. The most common injuries include tibial tubercle fractures, proximal tibia physeal fractures, and proximal tibia metaphyseal fractures; they may result from both low-energy and high-energy mechanisms. Nonoperative treatment is indicated for nondisplaced or adequately reduced fractures, while operative treatment is indicated for irreducible fractures or fractures with loss of adequate reduction. Complications of these injuries may include growth arrest, limb length discrepancy, angular deformity, vascular compromise, and compartment syndrome.
Predictors of Length of Physical Therapy Care for Infants With Congenital Torticollis
Authors: Aker Heather R. , Pierce Samuel R. , Moore Elizabeth S. , Martin Kathy
Published: December 2024

Purpose:

This study explored whether the type of torticollis, amount of tummy time or container time, participant age at examination, and Alberta Infant Motor Scales score influence the length of physical therapy care for infants with torticollis.

Methods:

Data for 149 participants were extracted from medical records for infants with torticollis who received care between November 2018 and November 2021.

Results:

Statistically significant correlations were found between length of care (LOC) and torticollis type, age at examination, active range of motion rotation deficit, and passive range of motion rotation deficit. A multiple regression model predicted LOC from age at examination in days, as well as passive and active rotation deficits.

Conclusion:

Higher passive and active rotation deficits lead to longer LOC. However, longer lengths of care were associated with younger ages at examination, different from earlier studies.
Transcranial direct current stimulation alleviates the pain severity in people suffering from knee osteoarthritis: a systematic review and meta-analysis
Authors: Dai Tian , Liu Meng , Bao Dapeng , Manor Brad , Zhou Junhong
Published: December 2024

Considerable research has shown the benefits of transcranial direct current stimulation (tDCS) for the alleviation of pain associated with knee osteoarthritis (KOA). Still, a large variance in study protocols and observations across publications exists. We here thus completed a systematic review and meta-analysis to comprehensively and quantitatively characterize the effects of tDCS on KOA-related pain. A search strategy based on the Population, Intervention, Comparison, Outcome, and Study design (PICOS) principle was used to obtain the publications in 7 databases. Studies exploring the effects of tDCS on KOA-related pain were screened, and eligible studies were included. Ten studies of 518 participants using Visual Analogue Scale or Numeric Rating Scale to assess pain were included in the systematic review, and 9 of them were included in meta-analysis. The quality of these studies was good. Compared to control, tDCS induced significant short-term improvements in KOA-related pain with medium heterogeneity (standardized mean difference [SMD] = −0.91, 95% confidence interval [−1.24, −0.58], P < 0.001, I2 = 61%). Subgroup analyses showed that both home-based (SMD = −1.32, 95% CI [−1.65, −0.99], P < 0.001, I
2 = 0%) and laboratory-based intervention (SMD = −0.66, 95% CI [−0.99, −0.33], P < 0.001, I
2 = 40%) with at least 5 sessions per week (SMD = −1.02, 95% CI [−1.41, −0.64], P < 0.001, I
2 = 65%) and/or with a total number of at least 10 sessions (SMD = −1.12, 95% CI [−1.51, −0.74], P < 0.001, I
2 = 59%) can induce maximum benefits for the alleviation of KOA-related pain. The results here showed that tDCS is of great promise to alleviate KOA-related pain. Still, future studies with more rigorous design are needed to confirm the observations from this work, which can ultimately help the determination of appropriate intervention protocol that can maximize such benefits.