bluuebunny/crossref_metadata_2025 huggingface dataset:
Qualitative analysis of pain impact in adult patients with X-linked hypophosphatemia
Authors: Nishime Nicole , Theriault Christopher , Feinn Richard , Macica Carolyn M
Published: January 2025

We previously reported pain as a predominant finding in adult patients with XLH. This study explored health-related quality-of-life using the 36-item Short Form survey instrument (SF-36v1) and pain experiences of adults with X-linked hypophosphatemia (XLH) through qualitative analysis of interviews with 15 patients (11 females, 4 males). Age-adjusted differences using SF-36 were lower than the general population in all domains of health-related quality of life, with significant differences notably related to physical function and pain. Ten themes emerged from semi-structured interviews: 1) Chronic and Variable Pain: Patients reported persistent pain of varying intensity and location; 2) Impact on Mobility and Daily Life: Pain severely restricted daily activities, affecting lifestyle, employment, and independence; 3) Pain Management: Patients used medications, physical therapy, lifestyle changes, alternative therapies, and assistive devices; 4) Healthcare and Accessibility Challenges: Access to appropriate care and treatments was limited by insurance issues and healthcare providers’ lack of XLH knowledge; 5) Emotional and Psychological Impact: Chronic pain and limitations led to social isolation, depression, and emotional burden; 6) Desire for Improved Information and Support: Patients sought better information, treatment, and community support; 7) Challenges with Physical Inactivity: Staying active was essential but difficult, as inactivity worsened pain; 8) Navigating Healthcare Services: Accessing therapy and insurance was often challenging; 9) Long-term Outlook and Concerns: Patients worried about disease progression and future health; and 10) Advocacy and Awareness: Increased public and medical awareness was needed to improve care. Although pain is not a universal experience within this population, it is a significant issue for many individuals with XLH. These data illustrate the profound impact of XLH on multiple life aspects underscoring the need for effective pain management strategies, better healthcare accessibility, supportive tools, and a more knowledgeable medical community to improve quality of life. Insights from this study will guide the development of a digital pain self-management intervention tailored to XLH patients to address these needs.
Eruptive YSOs in Cygnus-X: a mid-infrared variability study with NEOWISE and spicy
Authors: Morris C , Guo Z , Lucas P W , Miller N , Contreras Peña C , Kuhn M A
Published: January 2025

The mass accretion process controls pre-main-sequence evolution, although its intrinsic instability has yet to be fully understood, especially towards the protostellar stage. In this work, we have undertaken a thorough examination of the mid-infrared (MIR) variability of Spitzer-selected young stellar objects (YSOs) in the Cygnus-X star-forming region over the last decade, using the Near-Earth Object Wide-field Infrared Survey Explorer time series. This work compares two groups of young stars: embedded Class I objects, and the more evolved flat-spectrum/Class II sources. We report on 48 candidate eruptive variables within these groups, including 14 with characteristics that resemble the photometric behaviour of FUors. We also include an additional 20 YSOs, which are of a less certain categorization. We find the candidate FUors to be an order of magnitude more common among the younger Class I systems than more evolved objects. A large number of the identified short-duration eruptive YSOs display MIR colour behaviour that is redder-when-brighter, which contrasts with optically bright outbursts seen in YSOs. Finally, we note the unusual long-term rising behaviours of four Class I YSOs, with rise time-scales longer than 5 yr, which is far slower than $\sim$6–12 month time-scale for the majority of optically discovered FUors. Additionally, our broader investigation of MIR variability for embedded Class I YSOs shows that there is a higher incidence of high-amplitude variability for these stars, than is seen in Class II sources. This holds true for all variable Class I YSOs, not just the eruptive sources.
Imaging Biomarker Studies of Antipsychotic-Naïve First-Episode Schizophrenia in China: Progress and Future Directions
Authors: Zhang Wenjing , Qiu Changjian , Lui Su
Published: January 2025

Background and Hypothesis

Identifying biomarkers at onset and specifying the progression over the early course of schizophrenia is critical for better understanding of illness pathophysiology and providing novel information relevant to illness prognosis and treatment selection. Studies of antipsychotic-naïve first-episode schizophrenia in China are making contributions to this goal.

Study Design

A review was conducted for how antipsychotic-naïve first-episode patients were identified and studied, the investigated biological measures, with a focus on neuroimaging, and how they extend the understanding of schizophrenia regarding the illness-related brain abnormality, treatment effect characterization and outcome prediction, and subtype discovery and patient stratification, in comparison to findings from western populations. Finally, how biomarker studies should be conducted in the future was also discussed.

Study Results

Gray matter reduction has been most robust within temporo-frontal regions and cerebellum, whereas altered brain function has been most pronounced in cerebello-cortical connections and default mode network, each might be related to long-standing illness alterations and acute physiological alterations at measurement. By studying untreated patients, the progressive alterations in temporal and frontal regions and enlargements in bilateral putamen were found more likely effects of illness, not just treatment. Some of these changes were found with potential to predict clinical outcomes and differentiate biologically patient subgroups.

Conclusions

Mostly with data-driven approaches, the studies from China are helping identify candidate imaging biomarkers in schizophrenia that are related to early-stage illness, treatment effects, and biological subgroup differentiation. Future work is needed to translate these biomarkers for clinical application.
Impact of Sexual Intercourse on Frozen-Thawed Embryo Transfer Outcomes: A Randomized Controlled Trial
Authors: Hou Jin-Wei , Yuan Li-Hua , Cao Xian-Ling , Song Jing-Yan , Sun Zhen-Gao
Published: January 2025

(Abstracted from Contracept Reprod Med 2023;8:19

Spontaneous conception relies on many factors, one of which is the presence of seminal fluid inducing an immune response that assists pregnancy. This process, however, has not been studied in the context of assisted reproductive technology (ART) and assessed as to whether sexual intercourse is beneficial to the outcome.
Global, Regional, and National Burden of Low Back Pain
Authors: Cheng Mei , Xue Yinkai , Cui Min , Zeng Xianlin , Yang Cao , Ding Fan , Xie Lin
Published: January 2025

Study Design.

This was an observational study.

Objective.

Assessing the global burden of disease for low back pain (LBP) using the 2021 GBD (Global Burden of Disease) database.

Summary of Background Data.

LBP is a leading cause of workforce loss and disability. With societal aging and changes in lifestyle and work habits, the incidence of LBP is expected to rise. This study comprehensively analyzes the epidemiological trends of global LBP from 1990 to 2021.

Methods.

Data publicly available from the 2021 GBD study were utilized, and a systematic analysis was conducted to assess the global burden and epidemiological trends of LBP.

Results.

From 1990 to 2021, the age-standardized prevalence, incidence, and Years Lived with Disability (YLD) rates of LBP have slightly declined globally. However, the number of affected individuals, new cases, and YLD numbers have significantly increased, making LBP a leading cause of YLD in 2021. The number of affected individuals increases with age, peaking in both men and women between the ages of 50 and 54. Worldwide, women have a higher prevalence of LBP than men, and this increases with age, with both genders reaching peak prevalence between 80 and 84 years in 2021. Overall, over the past 3 decades, age-standardized YLD rates have shown a positive correlation with the Socio-demographic Index (SDI). In terms of region and nation, Tropical Latin America and Kingdom of Sweden have seen the greatest increase in age-standardized prevalence rates from 1990 to 2021.

Conclusion.

Globally, LBP remains a notable public health concern, carrying a consistently high burden. To alleviate the future impact of this disease, it is imperative to increase public awareness regarding its risk factors and to implement preventive measures.
Challenges of Contemporary Practice: Internists Maintaining Competency in Multiple Specialties
Authors: Weiner Jason J. , Durning Steven J. , Wildermuth Anne
Published: January 2025

Introduction:

Despite increasing physician specialization, high-quality continuing professional development is needed for continual mastery learning, especially focused on multiple specialties. Board certification is considered a surrogate for competency, and some stakeholders consider it suboptimally aligned with its primary purpose. We set to explore the motivation for continued education and competence in physicians who are board certified in multiple specialties.

Methods:

We performed a qualitative study using thematic analysis. Semistructured interviews were performed virtually. Landscapes of practice, an extension of communities of practice within sociocultural learning theory, was used as a theoretical framework.

Results:

Fifteen internists and their related subspecialties performing continual board certification completed the study. We identified six themes describing the underlying motivation for why physicians maintain competency in multiple medical specialties: Social responsibility, Promise of expertise, Enhanced job opportunities, Widened expertise, Professional requirements, and Personal fulfillment.

Discussion:

The landscape of medicine continues to evolve in how it is practiced. How a physician navigates this process, maintaining their competency, is a continuous lifelong learning process, and there are multiple ways. A portion of internal medicine physicians are motivated to practice in multiple specialties, recognizing the opportunities and challenges involved. The practical application of this study would include organizational-based education focused on hybrid learning (education explicitly focusing on overlapping or cross-discipline fields). Despite a plethora of educational opportunities, there is very little with the focus on cross-discipline education and training.
Separation Surgery Followed by Conformal Postoperative Spine Stereotactic Body Radiation Therapy Does Not Increase Risk of Adjacent Spine Level Progression in the Management of Spine Metastases
Authors: Strong Michael J. , Linzey Joseph R. , Goethe Peyton , Kathawate Varun , Tudrick Lila , Lee Johan , Ogunsola Oludotun , Zaki Mark M. , Ward Ayobami L. , Willet Noah , Joshi Rushikesh S. , Muhlestein Whitney , Saadeh Yamaan S. , North Robert Y. , Evans Joseph R. , Szerlip Nicholas J. , Jackson William C.
Published: January 2025

Objectives:

To determine if piecemeal separation surgery, in conjunction with smaller treatment volumes utilized with spine stereotactic radiation therapy (S-SBRT), increased the risk of adjacent level progression (ALP).

Methods:

We performed a retrospective analysis of a prospectively maintained database of adult spine oncologic patients who underwent SBRT to the spine at University of Michigan from 2010 to 2021. We compared ALP in patients undergoing SBRT who had pretreatment surgery with those who did not.

Results:

Four hundred and ninety-eight treatment sites were identified in 417 patients. Of these, 366 (73.5%) were treated with SBRT alone and 132 (26.5%) were treated with surgery followed by S-SBRT. Patients treated with SBRT alone were significantly older (63.3 y) compared with the surgery plus SBRT group (60.2 y; P=0.02). More radiosensitive histologies were treated with SBRT alone (34%) compared with 11% for the surgery plus SBRT group (P<0.001). Lesions treated in the surgery plus SBRT group had significantly more severe metastatic epidural spinal cord compression (65%) compared with the SBRT only group (8%) (P<0.001). Both infield progression (9.3% vs. 7.6%; P=0.43) and ALP (21.3% vs. 18.9%; P=0.37) were not significantly different between groups.

Conclusions:

Spine oncology patients treated with surgery followed by conformal postoperative S-SBRT had similar infield and ALP compared with patients receiving SBRT alone, suggesting that piecemeal separation surgery does not locally spread tumor cells, leading to an increased risk of ALP failure, and supporting the use of conformal postoperative S-SBRT.
Analysis of Research Waste in Phase III/IV Randomized Controlled Trials of Botulinum Toxin Type A
Authors: Chen Hongrui , Chang Shih-Jen , Zheng Yuanyang , Zhou Yanchun , Sun Bin , Hua Chen , Lin Xiaoxi
Published: January 2025

BACKGROUND

The application of randomized controlled trials (RCTs) outcomes of botulinum toxin type A (BoNT-A) to actual patient care faces a significant hurdle due to research waste (RW). This includes the results of RCTs that have not been published even 4 years after completion and those with insufficiently reported outcomes and design flaws. The prevalence of RW within BoNT-A-associated RCTs remains uncertain.

OBJECTIVE

To assess the extent of RW (non-publication, insufficient reporting, and design flaws) in BoNT-A RCTs.

METHODS

The authors searched the ClinicalTrials using ‘botulinum toxin type A’ as the keyword. They verified the publication status through PubMed and Scopus searches. The adequacy of reporting was assessed using the Consolidated Standards of Reporting Trials checklist, while design limitations were evaluated based on the risk of bias and systematic reviews.

RESULTS

Two hundred twenty-eight RCTs met the inclusion criteria for characteristics presentation. The RW analysis omitted 53 RCTs completed after June 2020, which remained unpublished. Of the 175 RCTs assessed, 98 were published, 71 demonstrated adequate reporting, and 25 had design limitations. Altogether, 118 RCTs (67.4%) exhibited at least 1 trait of RW. Multicenter designs and registrations post-2014 were independent protective factors against RW.

CONCLUSION

Within the 175 RCTs included in RW analysis, 67.4% of the studies presented some form of RW. The varied characteristics of the identified RW indicators offer essential insights for more rational planning of future BoNT-A RCTs.
Diagnostic approach to glomerular diseases
Authors: Babarinde Festus O. , Ogwu Nkechi P. , Babatunde Olusola D. , Babawale Emmanuel A. , Arrey Agbor Divine B. , AFuh Rechner N. , Okoye Osinachi K. , Jingwa Klein A. , Akpa Kenneth N. , Ogidan Afeez O. , Chiegboka Sobechukwu F. , Esangbedo Ikpembhosa J. , Onyedum Nwamaka N. , Ojeh Frankly G. , Ekwuluo Udodimma G. , Singh Priyanshu K. , Adegbola Michael O. , Odedairo Oluwaseun T. , Mohamed Mohammed S. , Kuttaplakkal Abdul Nazar Mohamed Shahzad , Nour Shafici Q. , Ighodaro Osazuwa T. , Elendu Chukwuka , Ngozi-Ibeh Jide K. , Nanim Winnifred , Akande Babatunde A. , Nwabueze Adaugo , Njoku Anthonia , Ikokwu Mary N. , Asue Msuurshima C. , Uzzi Consolata I. , Akinruli Oluwatosin A. , Ikeji Victor I. , Mba Orugbaoghene , Udoeze Chidi A. , Joseph Mary C. , Shode Omotola P.
Published: January 2025

Glomerular diseases are diagnostically complex due to their diverse clinical presentations and underlying etiologies. The diagnostic process begins with a detailed patient history and physical examination, focusing on signs and symptoms indicative of glomerular pathology. Essential laboratory evaluations include urinalysis, emphasizing proteinuria and urinary sediment analysis, and blood tests like serum creatinine and autoimmune markers, which are vital in narrowing differential diagnoses. Imaging modalities, such as renal ultrasound and computed tomography or magnetic resonance imaging scans, where appropriate, contribute additional information regarding renal structure and function. Renal biopsy remains the definitive diagnostic tool, often employed when noninvasive tests suggest significant pathology, guiding diagnosis and treatment strategies. The review advocates for a systematic, multidisciplinary approach to diagnosing and managing glomerular diseases. By elucidating these diagnostic principles, this article improves clinicians’ diagnostic accuracy and patient care in the context of glomerular diseases.
A novel uterine-preserving surgical technique for placenta accreta spectrum from Jakarta’s National Accreta Center: a retrospective cohort study
Authors: Purwosunu Yuditiya , Rumondang Amanda , Dilmy Muhammad A.F. , Saroyo Yudianto B. , Muskitta Nathalia I. , Siagian Natan K.P.
Published: January 2025

Introduction:

Placenta accreta spectrum is a significant life-threatening condition due to massive bleeding. Jakarta’s National Accreta Center has developed a novel uterine-preserving surgical technique called Jakarta Surgical Uterine Conservation as an alternative to hysterectomy. This study describes this novel technique and compares its perioperative outcomes with those of a standard hysterectomy.

Methods:

This novel and original surgical technique for conserving the uterus when managing placenta accreta spectrum used only a one-step surgery with one incision, followed by a U-shaped application for uterine reconstruction. This retrospective cohort study included all patients with placenta accreta spectrum who underwent the Jakarta Surgical Uterine Conservation technique or standard hysterectomy between January 2015 and December 2021. Bivariate analysis was performed using Pearson’s chi-square or Fisher’s exact test to compare the perioperative outcome comparisons between the two groups. The crude odds ratio was then calculated.

Results:

The two groups’ baseline demographic characteristics and risk factors were similar. The operation duration was shorter (odds ratio [OR] 5.085, 95% confidence interval [CI] 2.225–11.622, P < 0.001), and the risk of intensive care unit admission decreased (OR, 2.345; 95% CI, 1.184–4.647, P = 0.013) with the Jakarta Surgical Uterine Conservation technique compared to a standard hysterectomy.

Conclusion:

The Jakarta Surgical Uterine Conservation technique can be used to manage placenta accreta spectrum. It also shortens the operative duration and decreases the risk of ICU admission.
Comparison of Kinetic, Automated, Tangent Screen, and Novel Disposable Perimetry for the Evaluation of Dermatochalasis and Blepharoptosis
Authors: Rebollo Nicole P. , Hwang Catherine J. , Perry Julian D.
Published: January 2025

Purpose:

To compare a novel disposable ptosis visual field device to conventional perimetry devices for the evaluation of dermatochalasis and/or blepharoptosis.

Methods:

Forty patients from a single academic center participated in this prospective, observational study. Patients with dermatochalasis (skin resting on the eyelashes) and/or blepharoptosis (marginal reflex distance 1 ≤2 mm) were included. Each subject underwent untaped and taped perimetry using 4 visual field devices in random order: Goldmann visual field (GVF), automated Humphrey visual field (HVF), tangent screen (TS), and the novel visual field device (NVF). One eye was randomly selected, and McNemar tests and paired t tests were used to establish comparisons between devices.

Results:

The mean difference between untaped and taped central perimetry (in °) in the GVF, NVF, HVF, and TS was 26.5° ± 14.0°, 12.4° ± 8.5°, 9.6° ± 6.5°, and 9.6° ± 5.8°. The novel device detected a mean 2.9° greater difference than both the HVF (p = 0.083) and the TS (p = 0.062). The GVF, NVF, HVF, and TS detected a ≥12° difference in 90%, 50%, 39%, and 32.5% of eyes, respectively. The GVF detected a mean 14.1° greater difference than the novel device (p < 0.001). The GVF, NVF, HVF, and TS detected a ≥30% superior field occlusion in 98%, 73%, 55%, and 50% of eyes, respectively. There was no statistical difference in the ability of the NVF to detect a >12° difference or ≥30% superior field restriction compared with HVF or TS.

Conclusions:

The NVF is as reliable as the commonly used HVF and TS for the evaluation of visual obstruction due to blepharoptosis and dermatochalasis. The GVF is more sensitive than the other 3 devices. The novel disposable visual field device could allow for virtual visual field testing.
Accuracy of Intraocular Lens Power Calculation Based on Distance from Haptic to Principal Object Plane
Authors: Eom Youngsub , Yang Seul Ki , Woo Minji , Kim Jae-Ik , Choi Kwang Eon , Kim Dong Hyun , Lee Hwa , Suh Young-Woo , Song Jong Suk , Cooke David L
Published: January 2025

Purpose:

To investigate the impact of the distance from the most-anterior surface of the optic to the principal object plane (POP) and from the foremost haptic to the principal object plane (H-POP) on the intraocular lens (IOL) power calculation.

Setting:

A tertiary hospital.

Design:

Optical simulation and retrospective cross-sectional study.

Methods:

The optical simulation study plotted changes in the POP and H-POP as a function of IOL power using ICB00 IOL configuration data. The clinical study included 102 eyes of 102 patients implanted with ICB00 IOL to examine the correlation between changes in both the POP and the H-POP, and the prediction error calculated using the Barrett Universal II formula with varying IOL power.

Results:

The ICB00 IOL showed minor fluctuations in the POP (0.21 mm to 0.30 mm) with changing IOL power. The H-POP increased stepwise from 5.0 D, peaking at 0.60 mm at 16.0 D, then decreased to a minimum of 0.14 mm at 34.0 D. The prediction error graph primarily mirrored the pattern of changes in the H-POP rather than the POP with varying IOL power. Linear regression showed a significant myopic shift in prediction error as IOL power increased beyond 16.0 D (Y = –0.069X+1.420, R2=0.178, p<0.001).

Conclusion:

For the ICB00 IOL, the H-POP has more impact on IOL power calculation than the POP itself. For more accurate IOL power calculations, it is essential for all IOL manufacturers to provide comprehensive information on both optic and haptic geometries, which will enable the precise calculation of H-POP.
Influence of Fluid Intake on Biophysical Properties of the Stratum Corneum in Elderly Individuals: A Cross-Sectional Study
Authors: Amalia Rhida Sarly , Yusharyahya Shannaz Nadia , Nilasari Hanny , Sunardi Diana
Published: January 2025

Objective:

Water plays a crucial role in human health. Inadequate water intake can lead to various health issues, particularly dehydration in the elderly. The skin, constituting approximately 30.0% of the body’s surface area, is essential in preventing dehydration, and water contributes significantly to its resilience, elasticity, and durability. This study aimed to establish a definitive relationship between fluid intake and various biophysical properties of the stratum corneum in elderly Individuals.

Methods:

This cross-sectional study was conducted on individuals aged 65–80 years at the Elderly Social Institution Tresna Budi Mulia 3 in Jakarta, between April and August 2023. Correlation analysis (Pearson and Spearman tests) was used to evaluate relationships between variables, and non-parametric tests (Mann–Whitney and Friedman tests) were used to assess differences. Fluid intake was assessed over 7 days. On the 8th day, the hydration status of the stratum corneum was evaluated by examining their urine concentration, skin dryness through subjective symptoms, skin water loss based on the rate of water evaporation from the skin, and skin capacitance (SCap) according to the skin’s ability to retain moisture.

Results:

The study involved 67 subjects with a median age of 70 years. Multiple regression analysis showed that fluid intake significantly predicted the specified symptom sum score (SRRC) (coefficient = −9.15 × 10⁻5, P = 0.001), urine specific gravity (coefficient = −0.01, P = 0.016), and SCap (coefficient = 0.005, P = 0.022). Additionally, a statistically significant weak negative correlation was found between fluid intake and hydration status (P < 0.0001) and between fluid intake and SRRC (P < 0.0001). However, no significant correlation was observed between fluid intake and transepidermal water loss (P = 0.613) or SCap (P = 0.060).

Conclusion:

This study highlights the potential role of fluid intake in influencing hydration status among elderly individuals. While fluid intake is significantly associated with certain biophysical properties of the skin, it does not show a consistent correlation with all measures of skin hydration and moisture retention.
The use of continuous remimazolam and propofol for procedural sedation and analgesia during colonoscopy: A case series
Authors: Koch Rebecca , Coenen Wouter , Bisseling Tanya , Vaneker Michiel , van Eijk Lucas , Bruhn Jörgen
Published: January 2025

Rationale and patient concerns:

Propofol is the most frequently used sedative for procedural sedation and analgesia (PSA). However, side effects are cardiovascular and respiratory depression and pain on injection. Remimazolam is equally effective as propofol with improved hemodynamic stability and less respiratory depression and not painful on injection. However, propofol achieves a deeper level of sedation, suggesting that the addition of propofol to remimazolam may combine the best of both worlds. Continuous administration of remimazolam for PSA during colonoscopy has never been described. Here, we evaluate 11 cases in which the combination of continuous remimazolam and propofol with alfentanil is used for PSA during colonoscopy.

Diagnoses and interventions:

Eleven patients received intravenous remimazolam to induce sedation, followed by continuous infusion at varying rates to maintain sedation. A low dose of propofol was also administered, along with boluses of alfentanil for analgesia during the procedure.

Outcomes:

The combination of remimazolam, propofol, and alfentanil resulted in adequate sedation depth, quick emergence from sedation, and 100% amnesia for the procedure. Patients and physicians expressed high satisfaction with the approach. Vital signs were stable during the procedure, with minimal instances of decreased blood pressure and no significant oxygen desaturations. The combination of sedatives showed potential benefits, but further investigation through randomized controlled trials is necessary to confirm its advantages.

Lessons:

Continuous administration of remimazolam, propofol, and alfentanil during colonoscopy appears to be a promising option for PSA, offering effective sedation with relatively low risk of adverse effects.
Urinary Incontinence in Primary Care—The Gap Between Recommendations and Real World
Authors: Geynisman-Tan Julia , Cherupally Manisha , Alexandria Shaina J. , Brown Tiffany , Collins Sarah , Mathews Ashley , Pedamallu Havisha , Kenton Kimberly S. , Persell Stephen D.
Published: January 2025

(Abstracted from Urogynecology 2024;30:765–773

Lower urinary tract symptoms appear in a large percentage of women at some point in their lives, and represent a significant burden in health care and quality of life. Recent studies have reported this prevalence as high as 45% for urinary incontinence (UI) and 20% for pelvic floor disorders.
Pharmacotherapy for Agitation Management in a Pediatric Emergency Department
Authors: Brasel Kelsey , LaScala Elizabeth , Weeda Erin , Rarrick Christine
Published: January 2025

Objectives

In the treatment of agitation in a pediatric emergency department (PED), it is common to use once or as needed (PRN) medications when nonpharmacological management options have failed. Currently, there is limited available evidence on the treatment of pediatric agitation. The objective of this analysis was to characterize the prescribing practices of once or PRN medications for the treatment of agitation in a PED at an academic medical center.

Methods

This was a retrospective chart review of all encounters in which a patient was administered once or PRN medications for agitation treatment in the PED from July 1, 2021, to June 30, 2022. Once or PRN medications were defined as any medication in the antipsychotic, benzodiazepine, and barbiturate classes along with diphenhydramine, clonidine, ketamine, and guanfacine. The primary outcome was to describe the prescribing patterns of the most utilized agents for the treatment of agitation in the PED. Secondary outcomes were to assess effectiveness and safety of the agents utilized.

Results

We reviewed 109 patient encounters in which a once or PRN medication was used for agitation treatment. The most common initial regimens were benzodiazepine monotherapy (n = 47; 43%), antipsychotic monotherapy (n = 23; 21%), and concurrent use of an antipsychotic, benzodiazepine, and diphenhydramine (n = 16; 15%). Patients required another administration of a once or PRN medication within 5 to 120 minutes of initial administration 11% (n = 12) of the time. No patients required rapid sequence intubation and one patient (0.9%) needed treatment for extrapyramidal symptoms.

Conclusions

Results indicate that there is not a standard regimen choice in the treatment of agitation in the PED; however, benzodiazepine monotherapy was used most frequently. Few adverse events occurred. Further research is needed to identify the optimal regimen choice for patients presenting with agitation in a PED.
Severe Lymphopenia Predicts Poorer Survival in Patients With Rectal Cancer Undergoing Neoadjuvant Chemoradiation
Authors: Kim Daniel W. , Lee Grace , Cai Elise M. , Ryan David P. , Parikh Aparna R. , Allen Jill N. , Giantonio Bruce J. , Berger David L. , Kunitake Hiroko , Ricciardi Rocco , Cusack James C. , Roberts Hannah J. , Hong Theodore S. , Wo Jennifer Y.
Published: January 2025

Purpose

Chemoradiation-induced lymphopenia is common and associated with poorer survival in multiple solid malignancies. However, the association between chemoradiation-related lymphopenia and survival outcomes in rectal cancer is yet unclear. The objective of this study was to evaluate the prognostic impact of lymphopenia and its predictors in patients with rectal cancer undergoing neoadjuvant chemoradiation.

Methods

The inclusion criteria for this single-institution retrospective study were as follows: (1) biopsy-proven diagnosis of rectal adenocarcinoma, (2) receipt of neoadjuvant chemoradiation followed by surgery, and (3) absolute lymphocyte count available prior to and within 12 weeks of chemoradiation. In general, chemoradiation consisted of 5-fluorouracil or capecitabine and radiotherapy with 50.4 Gy over 28 fractions. Lymphopenia was graded according to the Common Terminology Criteria for Adverse Events version 5.0. The primary variable of interest was absolute lymphocyte count nadir within 12 weeks of chemoradiation, dichotomized by <500/μL (grade 3 or worse lymphopenia). The primary endpoint was overall survival. Cox modeling and Kaplan-Meier methods were used to perform survival analyses.

Results

A total of 193 patients were identified with a median follow-up of 68 months. Overall clinical stage was 2 in 21% and 3 in 76%. Median baseline lymphocyte count for the entire cohort was 1700/μL. One hundred ten patients (57%) experienced chemoradiation-related severe lymphopenia. Pathologic complete response rate was 21%; 83% received adjuvant chemotherapy. Lower baseline lymphocyte count was significantly associated with increased risk for chemoradiation-related severe lymphopenia (odds ratio, 1.71). On multivariable Cox regression analysis, chemoradiation-related severe lymphopenia was significantly associated with worse disease-free survival (hazard ratio, 2.64) and overall survival (hazard ratio, 4.32). Five-year overall survival was 79% versus 92%, and 5-year disease-free survival was 70% versus 86% in the cohort that experienced versus did not experience severe lymphopenia, respectively.

Discussion

Chemoradiation-induced lymphopenia is common and a prognostic marker of poorer survival in rectal cancer. Closer observation in high-risk patients and treatment modifications may be potential approaches to mitigating treatment-related lymphopenia. Our findings also suggest an important role of the host immunity in rectal cancer outcomes and support future studies investigating ways to reduce treatment-induced lymphopenia.
Treatment Crossover Following Advanced Therapy for Overactive Bladder Syndrome
Authors: Edge Preston , Yanek Lisa R. , Patterson Danielle , Chen Chi Chiung Grace , Handa Victoria L.
Published: January 2025

Importance

Patients deciding between advanced therapies for overactive bladder syndrome may be interested to know the likelihood of treatment crossover after sacral neuromodulation, intradetrusor OnabotulinumtoxinA, or percutaneous tibial nerve stimulation. Treatment crossover was defined as a switch from one advanced therapy to another.

Objectives

The aim of this study was to estimate the rate of treatment crossover after each advanced therapy for nonneurogenic overactive bladder syndrome. Our secondary objective was to compare medication use after each advanced therapy.

Study Design

Using claims data from the MarketScan database, privately insured women 18–65 years old with overactive bladder syndrome were identified for this retrospective cohort study. For all patients who received an advanced therapy between 2013 and 2019, we calculated the proportion who subsequently crossed over to a different advanced treatment. For each advanced therapy, we also calculated the proportion who subsequently utilized overactive bladder medication.

Results

We identified 7,231 adult women who underwent index advanced therapy for overactive bladder syndrome between 2013 and 2019. Treatment crossover occurred in 309 women (4.3%) and was significantly more likely following percutaneous tibial nerve stimulation (8.0%) compared to sacral neuromodulation (4.2%) or intradetrusor OnabotulinumtoxinA (2.6%, P < 0.01). Treatment crossover was also more likely following sacral neuromodulation compared to intradetrusor OnabotulinumtoxinA (P < 0.01). Medication use after advanced therapy was more common after percutaneous tibial nerve stimulation (29.2%) compared to intradetrusor OnabotulinumtoxinA (20.4%) or sacral neuromodulation (18.8%, P < 0.01).

Conclusions

Treatment crossover following advanced therapy for overactive bladder syndrome was uncommon but was significantly more likely after percutaneous tibial nerve stimulation. Medication use following advanced treatment occurred in a substantial minority in all cohorts.
Liver Injury as a Risk Factor for Post-Traumatic Venous Thromboembolism
Authors: Cobler-Lichter Michael D , Delamater Jessica M , Lyons Nicole B , Collie Brianna L , Meizoso Jonathan P , Pizano Louis R , Proctor Kenneth G , Namias Nicholas , Carter Nicholas H
Published: January 2025

Background:

Venous thromboembolism (VTE) remains a major source of morbidity and mortality in severely injured patients despite current methods of risk stratification and prophylaxis, suggesting incomplete understanding of VTE risk factors. Given the liver’s role in coagulation, we hypothesized that liver injury (LI) is associated with increased rates of VTE in severely injured patients.

Study Design:

The American College of Surgeons Trauma Quality Improvement Project database (TQIP) 2017-2021 was retrospectively reviewed for patients with a maximum abdominal Abbreviated Injury Score (AIS) ≥ 4 with or without LI. Transfers, burns, all deaths, and patients < 18 years of age were excluded. Logistic regression was performed to assess the independent effect of LI on development of pulmonary embolism (PE) and deep venous thrombosis (DVT) while controlling for potential confounding variables.

Results:

In 44,506 patients, there were 1,736 (3.9%) 890 (2.0%), and 18,642 patients (41.9%) with DVT, PE, and LI, respectively. After controlling for potential confounders, LI was independently associated with PE (aOR 1.279 [95% CI 1.088-1.504]) but was not associated with DVT (aOR 1.011 [95% CI 0.897-1.140]).

Conclusion:

In severely injured patients, LI is an independent predictor of PE, but not DVT, suggesting LI is the source of either emboli or a more complex locally prothrombotic focus leading to downstream thrombi in the lung without causing upstream systemic venous thrombi. Further work should focus on elucidation of mechanisms including the portal venous blood coagulation profile, endothelial injury in the liver, and the potential for stasis of venous blood traversing an injured liver as well as the role for including LI in VTE risk stratification.
Evolution of parasite transmission dispersion
Authors: MacDonald Hannelore , Bonhoeffer Sebastian , Regoes Roland
Published: January 2025

An open question in epidemiology is why transmission is often overdispersed, meaning that most new infections are driven by few infected individuals. For example, around 10% of COVID-19 cases cause 80% of new COVID-19 cases. This overdispersion in parasite transmission is likely driven by intrinsic heterogeneity among hosts, i.e. variable SARS-CoV-2 viral loads. However, host heterogeneity could also indirectly increase transmission dispersion by driving parasite adaptation. Specifically, transmission variation among hosts could drive parasite specialization to highly infectious hosts. Adaptation to rare, highly infectious hosts could amplify transmission dispersion by simultaneously decreasing transmission from common, less infectious hosts. This study considers whether increased transmission dispersion can be, in part, an emergent property of parasite adaptation to heterogeneous host populations. We develop a mathematical model using a Price equation framework to address this question that follows the epidemiological and evolutionary dynamics of a general host–parasite system. The results predict that parasite adaptation to heterogeneous host populations drives high transmission dispersion early in epidemics. Furthermore, parasite adaptation can maintain increased transmission dispersion at endemic equilibria if virulence differs between hosts in a heterogeneous population. More broadly, this study provides a framework for predicting how parasite adaptation determines transmission dispersion for emerging and re-emerging infectious diseases.
Tit-for-tat strategies drive growth and inequality in production economies
Authors: Branzei Simina , Mehta Ruta , Nisan Noam
Published: January 2025

We consider production economies where multiple agents make goods according to their inherent production recipe. Daily agents bring goods to the market along with a monetary budget that they allocate across these goods in competitive bids. Goods are distributed in proportion to the bids they attract, with sellers collecting the corresponding revenues. Agents then use their acquired bundles as raw ingredients for the next day’s production. We analyse a dynamic known as proportional response, where agents adjust their bids on goods proportionally to returns on past investments: a tit-for-tat like market behaviour. We show these dynamics lead to growth of the economy, whenever growth is feasible within the parameters of the model. The dynamics implicitly learn a key global feature of the network—the most efficient production cycles—through local interactions among the agents who communicate only with their immediate neighbours, with information flowing across the network edges. However, the dynamics also lead to unbounded inequality, i.e. very rich and very poor agents emerge and the gaps between their fortunes expand over time. We analyse several other phenomena, such as the existence of free-riding in star networks, where an agent may have growing fortune without participating in any efficient production cycle if they have strong enough connections with the centre.
Decoding ladybird’s colours: structural mechanisms of colour production and pigment modulation
Authors: Carrada Marzia , Haddad Mohamed , San José Luis , Agez Gonzague , Poumirol Jean-Marie , Magro Alexandra
Published: January 2025

This study investigates the mechanisms underlying colour production in the family Coccinellidae, focusing on two model species:A. bipunctata (L)andC. quatuordecimguttata (L). In this family, colours have traditionally been attributed primarily to pigments such as carotenoids and melanins. We propose an alternative perspective, considering the elytra as an integrated optical medium whose optical properties result from both its architectural design and the properties of its constituent materials, including matrix and pigments. In the present work, several methods were used, ranging from optical and electron microscopies, light-based techniques, to LC-HRMS analyses. Through local pigment analyses, microstructural examination of elytra, and modelling of interaction of elytra with light, we show that, while pigments are central to patterning and contribute to colour, overall colour also results from one or more physical mechanisms that may operate simultaneously. In the light of these results, we assume that the complex and diverse colouration in the Coccinellidae can only be elucidated by considering the interplay of pigments and the optical properties of the elytron cuticle.
A nonhuman primate model mirrors human congenital cytomegalovirus infection and reveals a spectrum of vertical transmission outcomes
Authors: Manuel Tabitha , Moström Matilda , Crooks Chelsea M. , Davalos Angel , Barfield Richard , Scheef Elizabeth , Kendall Savannah , Midkiff Cecily C. , Sprehe Lesli , Trexler Macey , Boquet Francis , Shroyer Monica , Danner Victoria , Doyle-Myers Lara , Weinbaum Carolyn , Mirza Anne , Lammi Stephen , Otero Claire , Lee Marissa R. , Rogers Layne W. , Granek Joshua , Owzar Kouros , Malouli Daniel , Früh Klaus , Kowalik Timothy , Chan Cliburn , Permar Sallie R. , Blair Robert V. , Kaur Amitinder
Published: January 2025

Congenital cytomegalovirus (cCMV) is the leading infectious cause of birth defects worldwide, yet immune determinants of protection to inform design of a maternal vaccine remain elusive. Here, we characterized the outcome of primary rhesus CMV (RhCMV) infection during pregnancy in an immune competent nonhuman primate (NHP) model. RhCMV DNA was detected in amniotic fluid and/or fetal tissues in six of 12 (50% placental transmission) CMV-naive rhesus macaque dams inoculated intravenously with RhCMV in early second trimester gestation. Widespread tissue dissemination dominated by one of two inoculated RhCMV strains was present in one fetus (8.3% cCMV disease). Placental RhCMV transmission was associated with elevated fetal and maternal plasma TNF-alpha and reduced maternal brain-derived neurotrophic factor and IL-10 levels. CMV exposure during pregnancy had a broad impact on the placenta and fetus even in the absence of congenital infection as evidenced by RhCMV infection at the maternal-fetal interface in all 12 dams, along with significantly reduced placental efficiency and fetal growth metrics compared to gestation-matched control pregnancies. This NHP model recapitulates key aspects of human cCMV and provides new insight into barriers and biomarkers of successful vertical transmission.

One sentence summary:The nonhuman primate model mirrors the epidemiology of human congenital CMV (cCMV) after primary infection and reveals its transmission bottlenecks.
Sequencing complete plasmids on Oxford Nanopore Technology Sequencers usingR2C2andChopper
Authors: Schimke Kayla D. , Vollmers Christopher
Published: January 2025

Plasmids are ubiquitous tools in molecular biology which are used for a large variety of experiments within academic and commercial labs.

Both new and old plasmids have to undergo sequencing-based analysis to determine whether or not they are functional, i.e. contain the correct insert in the correct backbone. While traditional Sanger sequencing based analysis was most often limited to the inserts, new high-throughput sequencing based methods and services can now provide the complete sequence of a plasmid. Currently available methods and services vary in throughput and cost.

Here, we adapted the Oxford Nanopore Technologies-based R2C2 sequencing method to - rapidly and at low cost - sequence complete plasmids, either individually or in a pool. We also developed an analysis pipeline, Chopper, that produces full-length plasmid sequences. We tested our workflow with commonly used plasmids we ordered from Addgene and produced highly accurate sequences for each plasmid from both their individual and pooled sequencing runs.
Comparative Patterns of Variation on the X Chromosome and Autosomes: The Role of the Breeding Sex Ratio
Authors: Spurley William J. , Payseur Bret A.
Published: January 2025

In many populations, unequal numbers of females and males reproduce each generation. This imbalance in the breeding sex ratio (BSR) shapes patterns of genetic variation on the sex chromosomes and the autosomes in distinct ways. Despite recognition of this phenomenon, effects of the BSR on some aspects of variation remain unclear, especially for populations with non-equilibrium demographic histories. To address this gap in the field, we used coalescent simulations to examine relative patterns of variation at X-linked loci and autosomal loci in populations spanning the range of BSR with historical changes in population size. Shifts in BSR away from 1:1 reduce nucleotide diversity and the number of unique haplotypes and increase linkage disequilibrium and the frequency of the most common haplotype, with contrasting effects on X-linked loci and autosomal loci. Strong population bottlenecks transform relationships between the BSR, the site frequency spectrum, and linkage disequilibrium while relationships between the BSR, nucleotide diversity, and haplotype characteristics are broadly conserved. Our findings indicate that evolutionary interpretations of variation on the X chromosome should consider the combined effects of the BSR and demographic history. The genomic signatures we report could be used to reconstruct these fundamental population parameters from genomic data in natural populations.

Significance Statement

The breeding sex ratio is a fundamental evolutionary parameter, but genomic analyses routinely assume it is 1:1. Our research characterizes the relationships between the breeding sex ratio and multiple facets of genomic variation and shows how these relationships change in the context of dynamic demographic histories. In doing so, we provide increasingly realistic expectations for patterns of X-linked and autosomal variation in population genomic datasets collected from natural populations.
Low level contamination confounds population genomic analysis
Authors: Ward Audrey K. , Scopel Eduardo F. C. , Shuman Brent , Momany Michelle , Bensasson Douda
Published: January 2025

Genome sequence contamination has a variety of causes and can originate from within or between species. Previous research focused primarily on cross-species contamination or on prokaryotes. This paper visualizes B-allele frequency to test for intra-species contamination, and measures its effects on phylogenetic and admixture analysis in two fungal species. Using a standard base calling pipeline, we found that contaminated genomes superficially appeared to produce good quality genome data. Yet as little as 5-10% genome contamination was enough to change phylogenetic tree topologies and make contaminated strains appear as hybrids between lineages (genetically admixed). We recommend the use of B-allele frequency plots to screen genome resequencing data for intra-species contamination.