bluuebunny/crossref_metadata_2025 huggingface dataset:
Beliefs and Practices on Depression Among Selected Filipino Indigenous Peoples: A Focused Ethnography
Authors: Moreno-Lacalle Rainier C. , Bangsal Myra R. , Bay-Ya Mae Rose T. , Erese Kristine Ann R. , Gabol Lourrie Ann P. , Geronimo Meriam M. , Legiralde Saintly Blaise B. , Lomandas Marfil Mae A. , Menzi Ma. Mae R. , Real Cici Donna L. , Solis John Michael Brico F. , Ufina Keanu U. , Lacanaria Mary Grace C.
Published: June 2023

Introduction:

Depression beliefs and practices among indigenous peoples are essential to creating responsive mental health services. The purpose of the study is to explore the cultural beliefs and practices on depression among the Ilocanos, Kankana-eys, and Maranaos indigenous peoples in the Philippines.

Method:

The study employed a focused ethnography research design. The study involved 41 ( N = 41) traditional healers and tribal leaders across Ilocano, Kankana-ey, and Maranao ethnic groups in the Philippine Islands. Interviews, reviews of records, and participant observation were used as data gathering tools.

Results:

Beliefs about depression include magico-spiritual influence, relational problems, economic pressure, and emotional domains. Practices were divided into three domains: preventive, curative, and rehabilitative interventions.

Discussion:

The depression beliefs and practices of Ilocano, Kankana-ey, and Maranao indigenous peoples are rooted in their tradition, culture, religion, and medical influences largely rooted in magico-spiritual approaches. These findings suggest the inclusion of culturally-based care to address depression.
The Value of Screening for a History of Incarceration in the Palliative Care Setting
Authors: Schnitter Joseph Michael , Hauser Joshua
Published: June 2023

The United States (US) has one of the highest rates of incarceration in the world. Due to the aging of the US population as a whole and limited opportunities for early release, the proportion of older people in prison continues to rise. Some correctional health systems have adopted geriatric and palliative care principles to better care for this aging population, many of whom die in prison. However, not everyone who grows old in prison will die behind bars. In this article, we explore existing literature that highlights the unique physical, cognitive, and psychosocial challenges that formerly incarcerated patients face. We proceed to argue that palliative care providers should screen for a history of incarceration to identify and address the needs of this patient population. We also offer strategies to create a safe, welcoming environment to discuss past traumas related to these patients’ time in prison.
Assessing the Agreement of Hypernasality and Audible Nasal Emission Ratings Between Audio-Recordings and a Clinic Setting
Authors: Williams Jessica L. , Cordero Kelly N. , Sitzman Thomas J.
Published: June 2023

Assess agreement of hypernasality and audible nasal emission (ANE) ratings between audio-recordings and a clinic setting.

Cross-sectional study using retrospective clinical recordings.

Audio-recording ratings by two trained speech language pathologists.

Percent agreement and intra- and inter-rater reliability of perceptual ratings.

Intra-rater reliability (AC2) of 167 audio-recorded speech samples for the primary and secondary raters, respectively, was 0.82 and 0.79 for hypernasality; for ANE, it was 0.57 and 0.75. Inter-rater reliability was 0.77 for hypernasality and 0.63 for ANE. When comparing ratings made from audio-recording versus the original clinical ratings, intra-rater reliability was 0.85 and 0.61 (primary and secondary rater, respectively) for hypernasality and 0.21 and 0.34 for ANE.

Ratings for hypernasality made from audio recordings were consistent with clinical evaluation, while ratings of ANE were not. ANE ratings made from audio recordings may not be a valid measure of velopharyngeal insufficiency speech characteristics.
Exploring Perceived Legal and Organizational Support and Attitudes on the Decision to Mediate or Arrest in Domestic Violence Cases: A Study Among Community and Criminal Justice Professionals in China
Authors: Zhao Ruohui , Zhang Hongwei , Wretman Christopher J. , Radtke Spenser R. , Rizo Cynthia Fraga , Kim Jeongsuk , Macy Rebecca J.
Published: June 2023

This study investigates factors related to the decision to (a) arrest or (b) mediate in domestic violence (DV) situations—nonmutually exclusive but highly differing decisions chosen a priori as being outcomes of interest. The sample included three types of professionals handling domestic violence cases in China: (a) Women's Federation (WF), (b) police, and (c) judicial personnel. The participants ( n = 817) responded to a vignette describing a DV incident. Logistic regression revealed that legal, organizational, and attitudinal factors were associated with decision-making and varied by group. The findings suggest training and detailed instructions on handling DV.
The final assault on nature: how the environmental crisis reinforces the civilizational crisis in Colombia
Authors: Steinhorst Samuel , Ossewaarde Marinus
Published: June 2023

Drawing on fieldwork, this article investigates the interplay between the environmental and civilizational crisis at the dawn of the Anthropocene. We explain how in the lower Cauca region in Colombia, possibilities of overcoming the environmental crisis are crushed by power constellations that delegitimize traditional ecological alternatives to extractive systems of governance and production. These alternatives are Indigenous and peasant knowledges and practices, which emerge from ontologies preceding and or later resisting European conquest and exploitation. Ecological alternatives may delineate paths to overcome the mastery of nature and subsequent environmental crisis, but they are under threat. Indeed, by privatizing and destroying ecosystems and violently displacing subsistence communities, extractivism is effectively eradicating entire cultures, valuable ecological knowledge, and perpetuating human suffering on a massive scale. We seek to explain how this process unfolds and also to identify possibilities for intervention and the empowerment of traditional ecological alternatives in the lower Cauca region.
Does Dietary Polyunsaturated Fatty Acid Intake Associate With Bone Mineral Density and Limb Structural Changes in Early Rheumatoid Arthritis?
Authors: Valner Annika , Müller Raili , Kull Mart , Põlluste Kaja , Lember Margus , Kallikorm Riina
Published: June 2023

Background:

Rheumatoid arthritis (RA) is an inflammatory disease that can result in bone erosion, lean mass lowering, and increase of fat mass without changes in body weight. The dietary consumption of polyunsaturated fatty acids (PUFAs) has been assessed in many studies due to their potential anti-inflammatory effect.

Aim:

The aim of this research was to identify if dietary intake of PUFAs associates with bone mineral density (BMD) and limb structural changes in early rheumatoid arthritis (ERA) compared to a population-based control group. The study was conducted because previous results have been insufficient.

Methods:

The study group consisted of 83 ERA patients and 321 control subjects. A dual-energy X-Ray absorptiometry (DXA) machine was used to measure hip, lumbar spine, and radius BMD, as well as arm and leg fat, lean, and bone mass. Dietary habits and inflammatory markers were assessed to evaluate the effects to BMD and limb structural changes.

Results:

In ERA subjects, higher dietary consumption of PUFAs was associated with a decrease in arm fat mass (b −28.17, P = .02) and possibly with higher lumbar BMD (b 0.008, P  = .058). Limb bone and lean mass changes were not associated with dietary intake of PUFAs.

Conclusion:

Balanced nutrition is essential. Consuming PUFAs could be beneficial in ERA preventing structural changes to hands, but additional research is needed.
Words matter: The use of generic “you” in expressive writing in an oncology setting
Authors: Snyder Stella , Milbury Kathrin , Wagner Richard , Cohen Lorenzo
Published: June 2023

The use of generic “you” (GY) in writing samples fosters psychological distancing and functions as a linguistic mechanism to facilitate emotion regulation. This method of creating psychological distance from the traumatic experience of cancer may be used by patients processing emotions. We used behavioral coding to analyze expressive writing samples collected from 138 cancer patients to examine the association between the use of “you” and cancer-related symptoms and psychological outcomes. Occurrences of GY were low, but our qualitative results showed how the use of GY could create a universal experience of cancer. The use of GY was not associated with cancer-related symptoms and depressive symptoms, but longitudinal analyses revealed that those using GY had fewer intrusive thoughts and avoidance behaviors across the follow-up period of 1, 4, and 10 months after the intervention. The development of psychological self-distancing prompts to use in writing interventions or as a clinical tool for cancer patients should be explored.
The field site as a religious frontier: Negotiating blasphemy accusations and reflexive tensions in Pakistan
Authors: Bilal Muhammad
Published: June 2023

In this article, I explore the reflexive tensions of a Muslim Anthropologist who conducted an ethnography of blasphemy in his own backyard exploring the predicament of fellow Christian Pakistanis in the face of growing blasphemy allegations. My authorial voice influenced by fluid emotional and religious frontiers raised certain critical questions such as how to reconcile my faith, personal judgment, and representation and how to keep a distinction between my positionality as a researcher and an advocate for my faith at a significant juncture when Islam and Pakistan became a focus of the world’s anxiety endangering religious freedom and safety of minorities. The article employs case study and narrative inquiry as a merged method to develop a critical narrative perspective on the blasphemy politics in Pakistan. I suggest that although my faith as an epistemological tool allowed me to investigate the intricacies and nuances surrounding the blasphemy accusations and victims’ plight, my ethnographic revelations could be subject to the severe criticism that I think is an inherent feature of postmodern ethnography.
Sharing the universal resources: Remarks on Honneth’s understanding of work
Authors: Jaeggi Rahel
Published: June 2023

Work is topic often neglected by contemporary philosophy. In academic political philosophy, this is due, among other things, to the dominance of analytic political liberalism and its bracketing of substantive questions regarding the “good” life. Surprisingly, however, even in critical theory there have been few exceptions to the general shunning of the question of work. That Axel Honneth, in his 2021 Benjamin Lectures, has now brought the subject out of the black box is an invaluable asset of his project. Nevertheless, I would like to ask two critical questions and make a suggestion. The first part of my inquiry concerns the side of the materiality of labor and expresses doubts whether the material basis Honneth seeks to recover is sufficiently material. The second part of my inquiry concerns the normative character of his understanding of work (i.e., the question of good work and the pathologies of labor) and suggests a Hegelian understanding of work, that is, work as participating in the universal resources of society. I argue that such an understanding would provide us with a much-needed sufficient basis for an encompassing but non-essentialist critique of the pathologies of labor.
Fluoroscopy-guided multiphase flat panel CT cisternography to diagnose complex skull base CSF leaks
Authors: Hendriks Eef Jacobus , Nasralla Mehran , Chung Emily , Nicholson Patrick Joseph , Andrade Barazarte Hugo Alberto , Farb Richard Ian
Published: June 2023

Skull base cerebrospinal fluid (CSF) leaks can be challenging to diagnose. We describe a first technical report on a fluoroscopy-guided multiphase flat panel computed tomography cisternography to diagnose a CSF leak in a complex postoperative anterior cranial fossa. The entry point, pathway of leakage, and exit point were visualized in detail. The feasibility and technical details are described. This technique could be an additional asset in the diagnostic work up of complex CSF leaks, not only of the anterior cranial fossa, but also complex CSF leaks of the middle cranial fossa.
A scoping review of tissue interposition flaps used in vesicovaginal fistulae repair
Authors: Serinçay Halime , Güler Hayrullah Uğur , Ulubayram Kezban , Mangır Naşide
Published: June 2023

Background:

Research on the use of tissue interposition flaps (TIFs) in vesicovaginal fistulae (VVF) repair is a broad area where a very wide range of natural and synthetic materials have been used. The occurrence of VVF is also diverse in the social and clinical settings, resulting in a parallel heterogeneity in the published literature on its treatment. The use of synthetic and autologous TIFs in VVF repair is not yet standardized with a lack of the most efficacious type and technique of the TIF.

Objectives:

The aim of this study was to systematically review all synthetic and autologous TIFs used in the surgical repair of VVFs.

Data sources and methods:

In this scoping review, the surgical outcomes of autologous and synthetic interposition flaps used in VVF treatment meeting the inclusion criteria were determined. We searched the literature using Ovid MEDLINE and PubMed databases between 1974 and 2022. Study characteristics were recorded, and data on the change in fistulae size and location, surgical approach, success rate, preoperative patient evaluation and outcome evaluation were extracted from each study independently by two authors.

Results:

A total of 25 articles that met the inclusion criteria were included in the final analysis. A total of 943 and 127 patients who had received autologous and synthetic flaps, respectively, were included in this scoping review. The fistulae characteristics were highly variable with regard to their size, complexity, aetiology, location and radiation. Outcome assessments of fistulae repair in included studies were mostly based on symptom evaluation. Physical examination, cystogram and methylene blue test were the methods in order of preference. Postoperative complications, such as infection, bleeding, donor site, pain, voiding dysfunction and other complications, were reported in patients after fistulae repair in all included studies.

Conclusion:

The use of TIFs in VVF repair was common especially in complex and large fistulae. Autologous TIFs appear to be the standard of care at the moment, and synthetic TIFs were investigated in prospective clinical trials in a limited number of selected cases. Evidence levels of clinical studies evaluating the effectiveness of interposition flaps were overall low.
An Online CMC–LC/MS Method for Screening Angiogenesis Promoting Components in Yiqi Fumai Lyophilization Injection (YQFM)
Authors: Xu Qing , Li Dekun , Wan Meixu , Zhang Yanxin , Li Zhi , Ju Aichun
Published: June 2023

Objective

In this study, an online CMC–LC/MS method was established in order to screen the active components of Yiqi Fumai lyophilization injection (YQFM) related to angiogenesis. The pro-angiogenic active components of YQFM were screened using this system and were then further verified.

Methods

The ECV304/CMC model coupled online with an HPLC–MS system was initially developed to screen, analyze, and identify the allergenic components of YQFM. A fraction was retained on the ECV304/CMC column, which was identified as ginsenoside Rb2. A cell proliferation assay and zebrafish intestinal microvascular model labeled with green fluorescence were used to detect the proliferation effect of ginsenoside Rb2.

Results

(1) The active component in YQFM, which was retained on the column, was ginsenoside Rb2. (2) Within a concentration range of 2.5–20 μg/mL, ginsenoside Rb2 was shown to promote the proliferation of ECV304 and EPCs cells and increase the area of sub-intestinal vessels in zebrafish.

Conclusion

Ginsenoside Rb2, the active component in YQFM, can promote angiogenesis. The ECV304/CMC-online-HPLC system may serve as an effective screening tool for the vasoactive components from the traditional Chinese medicine injection.
Multiple sclerosis and lower urinary tract symptoms: A survey of prevalence, characteristic and urological evaluations
Authors: Sharifiaghdas Farzaneh , Narouie Behzad , Taheri Maryam , Jalali Saba , Shalbafan Bita , Azadvari Mohaddeseh , Dadpour Mehdi , Rouientan Hamidreza , Ahmadzade Mohadese , Hanafi Bojd Hamideh
Published: June 2023

Objective:

Most multiple sclerosis patients have urological complications such as lower urinary tract symptoms. This study was conducted to evaluate the prevalence of these symptoms and whether they result in a urological evaluation.

Methods:

A cross-sectional study of 517 multiple sclerosis patients at Tehran’s referral multiple sclerosis center and neurology clinics between 2018 and 2022 was performed. Data were collected through interviews after patients completed informed consent forms. Urological examinations, including urine analysis and ultrasonography, were evaluated as final assessments. The data were analyzed using descriptive and inferential statistical tests in Statistical Package for Social Science.

Results:

Among all participants, the prevalence of lower urinary tract symptoms was 73% ( n = 384), with urgency (44.8% n = 232) being the most common symptom. The prevalence of intermittency was significantly higher among women ( p = 0.004). There was no gender-significant difference in terms of the prevalence of other symptoms ( p > 0.050). Lower urinary tract symptoms were significantly correlated with age, clinical course, disease duration, and disability ( p < 0.001). Additionally, 37.3% and 18.7% of patients with lower urinary tract symptoms, as well as 17.9% and 37.5% of patients with multiple sclerosis attacks, respectively, had undergone urine analysis and ultrasonography.

Conclusion:

Multiple sclerosis patients rarely undergo urological evaluations during the course of their disease. Proper assessment is essential as these symptoms are among the most detrimental manifestations of this disease.
Developing evidence based practice skills in youth justice
Authors: Trotter Chris , Evans Phillipa
Published: June 2023

A number of studies have found that when probation officers, and others who supervise young people and adults on community based orders, have good intervention skills their clients are more likely to be engaged in supervision and to have low recidivism rates. The skills include, role clarification, pro-social modelling, problem solving, cognitive and relationship skills. Little research has been done, however, on the development of these skills across whole organisations. This study aimed to examine the extent to which training and coaching of probation officers, across two state youth justice departments in Australia, improved the use of workers’ skills. Audio-tapes of worker/client interviews were provided to research staff before and after training and coaching. Analysis of the audio-tapes found a significant increase in the overall use of worker skills following the training and coaching. However, the increases in the skills applied largely to role clarification, rather than pro-social modelling, problem solving and cognitive skills.
Leg Length Discrepancy After Hip Fracture Repair is Associated With Reduced Gait Speed
Authors: Pearce Alexa N. , Sieber Frederick E. , Wang Nae-Yuh , Stambough Jeffrey B. , Stronach Benjamin M. , Mears Simon C.
Published: June 2023

Introduction

A negative correlation exists between functional outcomes and leg length discrepancy (LLD) following hip fracture repair. We have assessed the effects of LLD following hip fracture repair in elderly patients on 3-meter walking time, standing time, activities of daily living (ADL), and instrumental activities of daily living (IADL).

Methods

One hundred sixty-nine patients enrolled in the STRIDE trial were identified with femoral neck, intertrochanteric, and subtrochanteric fractures that were treated with partial hip replacement, total hip replacement, cannulated screws, or intramedullary nail. Baseline patient characteristics recorded included age, sex, body mass index Charlson comorbidity index (CCI) score. ADL, IADL, grip strength, sit-to-stand time, 3-meter walking time and return to ambulation status were measured at 1 year after surgery. LLD was measured on final follow-up radiographs by either the sliding screw telescoping distance or the difference from a trans-ischial line to the lesser trochanters, and was analyzed as a continuous variable using regression analysis.

Results

Eighty eight patients (52%) had LLD <5 mm, 55 (33%) between 5-10 mm and 26 subjects (15%) >10 mm. Age, sex, BMI, Charlson score, and ambulation status had no significant impact on LLD occurrence. Type of procedure and fracture type did not correlate with severity of LLD. Having a larger LLD was not found to have a significant impact on post-operative ADL ( P = .60), IADL ( P = .08), sit-to-stand time ( P = .90), grip strength ( P = .14) and return to former ambulation status ( P = .60), but did have a statistically significant impact on 3-meter walking time ( P = .006).

Discussion

LLD after hip fracture was associated with reduced gait speed but did not affect many parameters associated with recovery. Continued efforts to restore leg length after hip fracture repair are likely to be beneficial.
Adolescent Girls’ Early Marriage Intention and its Determinants in Eastern Ethiopia: A Social Norms Perspective
Authors: Abdurahman Dureti , Assefa Nega , Berhane Yemane
Published: June 2023

This study aimed to identify the association of perceived social norms with intention of early marriage practice among unmarried adolescent girls (13–17 years) in Kersa Demographic and Health Surveillance System. A community-based cross-sectional study was conducted during September–November 2019. Adolescent girls’ marriage intention was assessed using social norm measuring tools. The log-binomial model was used to identify factors associated with girls’ intention. Adjusted prevalence ratio along with 95% CIs was executed to determine the association of main independent variables with girl’s intention. A total of 859 adolescent girls participated in the study. The prevalence of intention to marry before the age of 18 years among adolescent girls was 44.47% (95% CI [0.41%, 0.48%]). The intention for an early marriage was higher among those with positive attitude toward early marriage, in those who believe that most people in their reference group conform to early marriage norms (empirical expectation), in those who believe that most people in their reference group expect them to conform to early marriage norms (normative expectation) and who fear sanction related to early marriage practices. Moreover, residence in urban areas and high educational level by girls and their parents was associated with reduced prevalence ratio. There is strong social norm in the community that promotes intention for an early marriage among adolescent girls in the study area. Hence, interventions that aim to reduce early marriage need to address local social norms.
Prevalence of little finger brachymesophalangia (BMP-V) in the Chinese population
Authors: Tang Nga Ping , Lam Gloria Yan Ting , Chow Esther Ching San
Published: June 2023

Objective

This study aims at determining the prevalence of little finger brachymesophalangia (BMP-V) in the Chinese ethnic population.

Methods

A retrospective study reviewing hand radiographs taken in United Christian Hospital from January 2011 to July 2016. Exclusion criteria included previous hand trauma, background history of genetic syndromes and non-Chinese ethnic origin. The radiographs were assessed with objective measurement using computer software and were defined BMP-V with the following criteria: (1) 5th MP length: 4th MP length <0.65 and (2) 5th MP length: 5th PP length <0.50. The radiographs would be included as BMP-V cases if they fulfil both criteria.

Results

A total of 563 hand radiographs in 394 patients (290 left hands and 273 right hands; 169 bilateral hands) were reviewed. The mean age (± standard deviation) was 51.3 ± 11.7 years (ranging from 25 to 69 years). Forty-four patients were identified to have BMP-V. The prevalence of BMP-V was found to be 11.2%. Clinodactyly with trapezoidal shape middle phalanx was found in 6.82% of the BMP-V cases. All subjects with bilateral hand radiographs showed symmetrical findings concerning the presence of BMP-V.

Conclusion

This is the first study to report the prevalence of brachymesophalangia-V in the Chinese adult population. The prevalence of BMP-V in the Chinese adult population was found to be 11.2%. It is lower than Japanese group but higher than other ethnic groups documented in other studies.
A Review of Clinical Signs and Symptoms of Imminent End-of-Life in Individuals With Advanced Illness
Authors: Ijaopo Ezekiel Oluwasayo , Zaw Khin Maung , Ijaopo Ruth Oluwasolape , Khawand-Azoulai Mariana
Published: June 2023

Background: World population is not only aging but suffering from serious chronic illnesses, requiring an increasing need for end-of-life care. However, studies show that many healthcare providers involved in the care of dying patients sometimes express challenges in knowing when to stop non-beneficial investigations and futile treatments that tend to prolong undue suffering for the dying person. Objective: To evaluate the clinical signs and symptoms that show end-of-life is imminent in individuals with advanced illness. Design: Narrative review. Methods: Computerized databases, including PubMed, Embase, Medline,CINAHL, PsycInfo, and Google Scholar were searched from 1992 to 2022 for relevant original papers written in or translated into English language that investigated clinical signs and symptoms of imminent death in individuals with advanced illness. Results: 185 articles identified were carefully reviewed and only those that met the inclusion criteria were included for review. Conclusion: While it is often difficult to predict the timing of death, the ability of healthcare providers to recognize the clinical signs and symptoms of imminent death in terminally-ill individuals may lead to earlier anticipation of care needs and better planning to provide care that is tailored to individual’s needs, and ultimately results in better end-of-life care, as well as a better bereavement adjustment experience for the families.
Antibody-mediated antigen loss switches augmented immunity to antibody-mediated immunosuppression
Authors: Jajosky Ryan P. , Patel Kashyap R. , Allen Jerry William L. , Zerra Patricia E. , Chonat Satheesh , Ayona Diyoly , Maier Cheryl L. , Morais Dominique , Wu Shang-Chuen , Luckey C. John , Eisenbarth Stephanie C. , Roback John D. , Fasano Ross M. , Josephson Cassandra D. , Manis John P. , Chai Li , Hendrickson Jeanne E. , Hudson Krystalyn E. , Arthur Connie M. , Stowell Sean R.
Published: June 2023

Antibodies against fetal red blood cell (RBC) antigens can cause hemolytic disease of the fetus and newborn (HDFN). Reductions in HDFN due to anti-RhD antibodies have been achieved through use of Rh immune globulin (RhIg), a polyclonal antibody preparation that causes antibody-mediated immunosuppression (AMIS), thereby preventing maternal immune responses against fetal RBCs. Despite the success of RhIg, it is only effective against 1 alloantigen. The lack of similar interventions that mitigate immune responses toward other RBC alloantigens reflects an incomplete understanding of AMIS mechanisms. AMIS has been previously attributed to rapid antibody-mediated RBC removal, resulting in B-cell ignorance of the RBC alloantigen. However, our data demonstrate that antibody-mediated RBC removal can enhance de novo alloimmunization. In contrast, inclusion of antibodies that possess the ability to rapidly remove the target antigen in the absence of detectable RBC clearance can convert an augmented antibody response to AMIS. These results suggest that the ability of antibodies to remove target antigens from the RBC surface can trigger AMIS in situations in which enhanced immunity may otherwise occur. In doing so, these results hold promise in identifying key antibody characteristics that can drive AMIS, thereby facilitating the design of AMIS approaches toward other RBC antigens to eliminate all forms of HDFN.
Mutations in atypical hemolytic uremic syndrome provide evidence for the role of calcium in complement factor I
Authors: Java Anuja , Atkinson John , Hu Zheng , Pozzi Nicola
Published: June 2023

Atypical hemolytic uremic syndrome (aHUS) is a rare thrombotic microangiopathy. Genetic variants in complement proteins are found in ≈60% of patients. Of these patients, ≈15% carry mutations in complement factor I (CFI). Factor I (FI) is a multidomain serine protease that cleaves and thereby inactivates C3b and C4b in the presence of cofactor proteins. Crystal structures have shown that FI possesses 2 calcium-binding domains, low-density lipoprotein receptor class A (LDLRA) 1 and LDLRA2. Yet, the role of calcium in FI is unknown. We determined that 9 genetic variants identified in aHUS (N151S, G162D, G188A, V230E, A240G, G243R, C247G, A258T, and Q260D) cluster around the calcium-binding site of LDLRA1. Using site-directed mutagenesis, we established that the synthesis of all, except A258T, was impaired, implying defective protein folding, perhaps due to loss of calcium binding. To further explore this possibility, we generated 12 alanine mutants that coordinate with the calcium in LDLRA1 and LDLRA2 (K239A, D242A, I244A, D246A, D252A, E253A, Y276A, N279A, E281A, D283A, D289A, and D290A) and are expected to perturb calcium binding. Except for K239A and Y276A, none of the mutants was secreted. These observations suggest that calcium ions play key structural and functional roles in FI.
Representation of the population in need for pivotal clinical trials in lymphomas
Authors: Casey Mycal , Odhiambo Lorriane , Aggarwal Nidhi , Shoukier Mahran , Islam K. M. , Cortes Jorge
Published: June 2023

Despite the advances in cancer outcomes, significant health disparities persist. Several new agents have been recently approved for treatment of lymphomas, leading to improved outcomes. Extending the benefits of these new agents starts by adequate enrollment of all affected patient populations. This study aimed to evaluate the extent to which randomized controlled trials (RCTs) match the demographic and geographic diversity of the population affected by lymphoma. Two Food and Drug Administration databases, clinicaltrials.gov, and relevant primary manuscripts were reviewed for drug approval data and demographic representation in RCTs for classical Hodgkin lymphoma (cHL) and non-Hodgkin lymphoma. Maps showing the distribution and frequency of trial participation relative to disease burden, insurance status, and racial representation were created. Black, Hispanic, and female patients were significantly underrepresented in the RCTs for lymphoma compared with that for the disease burden (3.6% [95% confidence interval (CI), 2.8-5.4] vs 14.6% [95% CI, 13.8-15.3]; 6.7% [95% CI, 5.5-7.9] vs 16.3% [95% CI, 15.5-17.1]; and 39.1% [95% CI, 37.3-40.9] vs 42.7% [95% CI, 42.3-43.1], respectively). White and male patients were overrepresented. More counties with higher mortality rates and racial minority representation had low access to the trials, particularly for cHL in the southern region of the United States. There are significant racial misrepresentations in pivotal RCTs in the United States, and geographic distribution of these trials may not provide easy access to all patients in need. Disparities in enrollment should be corrected to make results applicable to all populations.
Fixed-duration venetoclax plus obinutuzumab improves quality of life and geriatric impairments in FCR-unfit patients with CLL
Authors: van der Straten Lina , Stege Claudia A. M. , Kersting Sabina , Nasserinejad Kazem , Dubois Julie , Dobber Johan A. , Mellink Clemens H. M. , van der Kevie-Kersemaekers Anne-Marie F. , Evers Ludo M. , de Boer Fransien , Koene Harry R. , Schreurs John , van der Klift Marjolein , Velders Gerjo A. , van der Spek Ellen , van der Straaten Hanneke M. , Hoogendoorn Mels , van Gelder Michel , Posthuma Eduardus F. M. , Visser Hein P. J. , Houtenbos Ilse , Idink Cecile A. M. , Issa Djamila E. , Dompeling Ellen C. , van Zaanen Henk C. T. , Veelken J. Hendrik , Levenga Henriette , Tick Lidwine W. , Terpstra Wim E. , Tonino Sanne H. , Westerweel Peter E. , Langerak Anton W. , Kater Arnon P. , Levin Mark-David
Published: June 2023

Chronic lymphocytic leukemia (CLL)–related symptoms and morbidity related to the advanced age at diagnosis impairs the well-being of older adult patients. Therefore, it is essential to tailor treatment according to geriatric characteristics and aim for an improvement in health-related quality of life (HRQoL) as a primary treatment goal. In the HOVON139/GiVe trial, 12 cycles of fixed-duration venetoclax plus obinutuzumab (Ven-O) were shown to be effective and tolerable in FCR (fludarabine, cyclophosphamide, rituximab)-unfit patients with CLL (n = 67). However, prolonged venetoclax exposure as consolidation treatment led to increased toxicity with limited effect on minimal residual disease. To assess the impact of geriatric assessment on treatment outcomes and the patients’ HRQoL, patient-reported outcomes (PROs), including function, depression, cognition, nutrition, physical performance, muscle parameters, comorbidities, and the European Organization for Research and Treatment of Cancer C30 and CLL17 questionnaires were assessed. At baseline, geriatric impairments were present in >90% of patients and ≥2 impairments present in 60% of patients predicted grade ≥3 nonhematological toxicity. During treatment, the number of geriatric impairments diminished significantly and clinically relevant improvements in HRQoL subscales were reached for global health status, physical functioning, role functioning, emotional functioning, fatigue, dyspnea, physical condition or fatigue, and worries or fears related to health and functioning. These improvements were comparable for patients receiving venetoclax consolidation and patients in whom treatment could mostly be discontinued. Collectively, frontline fixed-duration Ven-O improves overall PROs in older, unfit patients with CLL with and without geriatric impairments. This study was registered at EudraCT as 2015-004985-27 and the Netherlands Trial Register as NTR6043.
Comparison of four different screw configurations for the fixation of Fulkerson osteotomy: a finite element analysis
Authors: Aykanat Faruk , Kose Ozkan , Guneri Bulent , Celik H. Kursat , Cakar Albert , Tasatan Ersin , Ulmeanu Mihaela-Elena
Published: June 2023

Background

Conventionally, two 4.5 mm cortical screws inserted toward the posterior tibial cortex are usually advocated for the fixation of Fulkerson osteotomy. This finite element analysis aimed to compare the biomechanical behavior of four different screw configurations to fix the Fulkerson osteotomy.

Materials and methods

Fulkerson osteotomy was modeled using computerized tomography (CT) data of a patient with patellofemoral instability and fixed with four different screw configurations using two 4.5 mm cortical screws in the axial plane. The configurations were as follows: (1) two screws perpendicular to the osteotomy plane, (2) two screws perpendicular to the posterior cortex of the tibia, (3) the upper screw perpendicular to the osteotomy plane, but the lower screw is perpendicular to the posterior cortex of the tibia, and (4) the reverse position of the screw configuration in the third scenario. Gap formation, sliding, displacement, frictional stress, and deformation of the components were calculated and reported.

Results

The osteotomy fragment moved superiorly after loading the models with 1654 N patellar tendon traction force. Since the proximal cut is sloped (bevel-cut osteotomy), the osteotomy fragment slid and rested on the upper tibial surface. Afterward, the upper surface of the osteotomy fragment acted as a fulcrum, and the distal part of the fragment began to separate from the tibia while the screws resisted the displacement. The resultant total displacement was 0.319 mm, 0.307 mm, 0.333 mm, and 0.245 mm from the first scenario to the fourth scenario, respectively. The minimum displacement was detected in the fourth scenario (upper screw perpendicular to the osteotomy plane and lower screw perpendicular to the posterior tibial cortex). Maximum frictional stress and maximum pressure between components on both surfaces were highest in the first scenario (both screws perpendicular to the osteotomy plane).

Conclusions

A divergent screw configuration in which the upper screw is inserted perpendicular to the osteotomy plane and the lower screw is inserted perpendicular to the posterior tibial cortex might be a better option for the fixation of Fulkerson osteotomy.

Level of evidence Level V, mechanism-based reasoning.
Factors associated with mortality after proximal femoral fracture
Authors: Walter Nike , Szymski Dominik , Kurtz Steve , Alt Volker , Lowenberg David W. , Lau Edmund , Rupp Markus
Published: June 2023

Proximal femoral fractures are a serious complication, especially for elderly patients. Therefore, we have aimed to answer the following research question: What is the postfracture mortality rate in the elderly population and what are associated risk factors? For this, proximal femoral fractures that occurred between 1 January 2009 and 31 December 2019 were identified from the Medicare Physician Service Records database. The Kaplan–Meier (KM) method with the Fine and Gray subdistribution adaptation was used to determine rates of mortality. A semiparametric Cox regression model was applied, incorporating 23 measures as covariates to identify risk factors. The estimated 1 year mortality rate was 26.8% after head/neck fracture, 28.2% after intertrochanteric fracture, and 24.2% after subtrochanteric fracture. Male sex, age over 70 years, chronic obstructive pulmonary disease (COPD), cerebrovascular disease, chronic kidney disease, a concomitant fracture, congestive heart failure, diabetes mellitus, hypertension, insulin use, ischemic heart disease, morbid obesity, osteoporosis, tobacco dependence, and median household income were determined as risk factors for increased mortality. An early assessment of individual risk factors accessible for therapeutic treatment is crucial in the management of proximal femur fractures to aid in attempts at reducing the high mortality apparent in the elderly US population.
The DNA methylation status of the serotonin metabolic pathway associated with reproductive inactivation induced by long-light exposure in Magang geese
Authors: Liu Jiaxin , Xu Yanglong , Wang Yushuai , Zhang Jinning , Fu Yuting , Liufu Sui , Jiang Danli , Pan Jianqiu , Ouyang Hongjia , Huang Yunmao , Tian Yunbo , Shen Xu
Published: June 2023

Background

Domestic geese are seasonal breeders and have the lowest reproductive capacity among all poultry species. Magang geese is a topical short-day breeder, short photoperiod exposure stimulates its reproductive activity while long photoperiod inhibits. To explore epigenetic change that could influence reproductive activity, we performed whole genome bisulfite sequencing and transcriptome sequencing in the hypothalamus at three reproductive stages during long-light exposure in male Magang geese.

Results

A total number of 10,602 differentially methylated regions (DMRs) were identified among three comparison groups. We observed that the vast majority of DMRs were enriched in intron regions. By integrating the BS-sequencing and RNA-seq data, the correlation between methylation changes of CG DMRs and expression changes of their associated genes was significant only for genes containing CG DMRs in their intron. A total of 278 DMR-associated DEGs were obtained among the three stages. KEGG analysis revealed that the DMR-associated DEGs were mainly involved in 11 pathways. Among them, the neuroactive ligand-receptor interaction pathway was significantly enriched in both two comparisons (RA vs.RD and RD vs.RI); the Wnt signaling pathway, apelin signaling pathway, melanogenesis, calcium signaling pathway, focal adhesion, and adherens junction were significantly enriched in the RA vs. RI comparison. In addition, the expression level of two serotonin-metabolic genes was significantly altered during reproductive axis inactivation by the methylation status of their promoter region (TPH2) and intron region (SLC18A2), respectively. These results were confirmed by Bisulfite sequencing PCR (BSP), pyrosequencing, and real-time qPCR, indicating that serotonin metabolic signaling may play a key role in decreasing the reproductive activity of Magang geese induced by long-light exposure. Furthermore, we performed a metabolomics approach to investigate the concentration of neurotransmitters among the three stages, and found that 5-HIAA, the last product of the serotonin metabolic pathway, was significantly decreased in the hypothalamus during RI.

Conclusions

Our study reveals that the methylation status of the serotonin metabolic pathway in the hypothalamus is associated with reproductive inactivation, and provided new insight into the effect of DNA methylation on the reproductive regulation of the hypothalamus in Magang geese.
Homoeologous evolution of the allotetraploid genome of Poa annua L.
Authors: Benson Christopher W. , Sheltra Matthew R. , Maughan Peter J. , Jellen Eric N. , Robbins Matthew D. , Bushman B. Shaun , Patterson Eric L. , Hall Nathan D. , Huff David R.
Published: June 2023

Background

Poa annua (annual bluegrass) is an allotetraploid turfgrass, an agronomically significant weed, and one of the most widely dispersed plant species on earth. Here, we report the chromosome-scale genome assemblies of P. annua’s diploid progenitors, P. infirma and P. supina, and use multi-omic analyses spanning all three species to better understand P. annua’s evolutionary novelty.

Results

We find that the diploids diverged from their common ancestor 5.5 – 6.3 million years ago and hybridized to form P. annua ≤ 50,000 years ago. The diploid genomes are similar in chromosome structure and most notably distinguished by the divergent evolutionary histories of their transposable elements, leading to a 1.7 × difference in genome size. In allotetraploid P. annua, we find biased movement of retrotransposons from the larger (A) subgenome to the smaller (B) subgenome. We show that P. annua’s B subgenome is preferentially accumulating genes and that its genes are more highly expressed. Whole-genome resequencing of several additional P. annua accessions revealed large-scale chromosomal rearrangements characterized by extensive TE-downsizing and evidence to support the Genome Balance Hypothesis.

Conclusions

The divergent evolutions of the diploid progenitors played a central role in conferring onto P. annua its remarkable phenotypic plasticity. We find that plant genes (guided by selection and drift) and transposable elements (mostly guided by host immunity) each respond to polyploidy in unique ways and that P. annua uses whole-genome duplication to purge highly parasitized heterochromatic sequences. The findings and genomic resources presented here will enable the development of homoeolog-specific markers for accelerated weed science and turfgrass breeding.
Long-wave opsin involved in body color plastic development in Nilaparvata lugens
Authors: Lu Jia-Bao , Li Ze-Dong , Ye Zhuang-Xin , Huang Hai-Jian , Chen Jian-Ping , Li Jun-Min , Zhang Chuan-Xi
Published: June 2023

Background

As one of the components of visual photopigments in photoreceptor cells, opsin exhibits different spectral peaks and plays crucial roles in visual function. Besides, it is discovered to evolve other functions despite color vision. However, research on its unconventional function is limited nowadays. With the increase in genome database numbers, various numbers and types of opsins have been identified in insects due to gene duplications or losses. The Nilaparvata lugens (Hemiptera) is a rice pest known for its long-distance migration capability. In this study, opsins were identified in N. lugens and characterized by genome and transcriptome analyses. Meanwhile, RNA interference (RNAi) was carried out to investigate the functions of opsins, and then the Illumina Novaseq 6000 platform-based transcriptome sequencing was performed to reveal gene expression patterns.

Results

Four opsins belonging to G protein-coupled receptors were identified in the N. lugens genome, including one long-sensitive opsin (Nllw) together with two ultraviolet-sensitive opsins (NlUV1/2) and an additional new opsin with hypothesized UV peak sensitivity (NlUV3-like). A tandem array of NlUV1/2 on the chromosome suggested the presence of a gene duplication event, with similar exons distribution. Moreover, as revealed by spatiotemporal expression, the four opsins were highly expressed in eyes with age-different expression levels. Besides, RNAi targeting each of the four opsins did not significantly affect the survival of N. lugens in phytotron, but the silencing of Nllw resulted in the melanization of body color. Further transcriptome analysis revealed that silencing of Nllw resulted in up-regulation of a tyrosine hydroxylase gene (NlTH) and down-regulation of an arylalkylamine-N-acetyltransferases gene (NlaaNAT) in N. lugens, demonstrating that Nllw is involved in body color plastic development via the tyrosine-mediated melanism pathway.

Conclusions

This study provides the first evidence in a Hemipteran insect that an opsin (Nllw) takes part in the regulation of cuticle melanization, confirming a cross-talk between the gene pathways underlying the visual system and the morphological differentiation in insects.
Inter-provincial variation in older home care clients and their pathways: a population-based retrospective cohort study in Canada
Authors: Mitchell Lori , Poss Jeffrey , MacDonald Martha , Burke Rosanne , Keefe Janice M.
Published: June 2023

Background

In Canada, publicly-funded home care programs enable older adults to remain and be cared for in their home for as long as possible but they often differ in types of services offered, and the way services are delivered. This paper examines whether these differing approaches to care shape the pathway that home care clients will take. Older adult client pathways refer to trajectories within, and out of, the home care system (e.g., improvement, long term care (LTC) placement, death).

Methods

A retrospective analysis of home care assessment data (RAI-HC was linked with health administrative data, long-term care admissions and vital statistics in Nova Scotia Health (NSH) and Winnipeg Regional Health Authority (WRHA). The study cohort consists of clients age 60 + years, admitted to home care between January 1, 2011 to December 31, 2013 and up to four years from baseline. Differences in home care service use, client characteristics and their pathways were tested across the two jurisdictions overall, and among the four discharge streams within jurisdictions using t-tests and chi-square tests of significance.

Results

NS and WHRA clients were similar in age, sex, and marital status. NS clients had higher levels of need (ADL, cognitive impairment, CHESS) at base line and were more likely discharged to LTC (43% compared to 38% in WRHA). Caregiver distress was a factor correlated with being discharged to LTC. While a third remained as home care clients after 4 years; more than half were no longer in the community – either discharged to LTC placement or death. Such discharges occurred on average at around two years, a relatively short time period.

Conclusions

By following older clients over 4 years, we provide enhanced evidence of client pathways, the characteristics that influence these paths, as well as the length of time to the outcomes. This evidence is central to identification of clients at risk in the community and aids in planning for future home care servicing needs that will allow more older adults to remain living in the community.