bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding and Framing Change in Islamic Law: Potentials and Possible Pitfalls of the Concepts of Canonization and Codification
Authors: Hovden Eirik
Published: June 2024

Conservative and populist notions of Islamic law, or Sharīʿa, emphasize its immutability. While the textual nature of traditional Islamic jurisprudence supports this conception, academic research in recent decades demonstrates that Islamic law saw constant change and development. We also witness an increasing acknowledgement that several processes of change do not always follow the rich and advanced emic narratives and theories of how change allegedly did or should happen. The possibility of change is also intimately connected to theories of authority, where normative and descriptive models may give different pictures. Several historians and anthropologists of Islamic law have resorted to ‘canonization’ and ‘codification’ as concepts employed to understand and frame significant change, partly intending to create an analytical distance to the study object, unrestricted by the Islamic tradition. While the two concepts have hitherto been employed separately, they have one thing in common: their focus on selection and authorization. This article will first demonstrate how these concepts have been used in Islamic legal studies and then further argue that by juxtaposing and comparing these two concepts, new insights can be gained regarding their potentials and pitfalls.
Users involvement in the electronic health information systems development process in Uganda: what is missing in relation to requirements gathering and analysis
Authors: Akello Christine Kalumera , Nabukenya Josephine
Published: June 2024

User involvement in the electronic health information systems (eHIS) development process is crucial for gathering and analysing requirements that accurately reflect user needs. This is because their involvement is linked to the gathering and analysis of requirements that align with user needs. However, several studies reveal that there is still limited user involvement during these crucial phases, leading to the development of ineffective and inefficient systems that do not reflect user needs. Thus, this study explored how users were involved in the requirements gathering and analysis phases during eHIS development, with an aim of identifying the missing elements that hindered the design of more effective and effective eHIS. A cross-sectional survey, encompassing secondary and primary users, explored their involvement in the requirements gathering, analysis and design phases, using both open-ended and close ended questionnaires. Respondents (n = 140) were purposively selected from 20 organizations in northern and central Uganda. Data were cleaned and analysed using Microsoft Excel. The findings revealed a dominant use of a top-down approach, favouring the capture of high-level requirements at the Ministry of Health level, and among implementing partners. However, less attention was given to gathering and analysing requirements from facility-level users. Even when collected, primary users reported that their opinions and recommendations were often ignored/disregarded, resulting in eHIS designs with usability-related challenges. This study underscores the critical need for active user involvement in the early stages of eHIS development to ensure alignment with user needs and work practices.
Mary Magdalene in Early Modern Visual and Material Culture
Authors: Moseley-Christian Michelle
Published: June 2024

The fragmented narrative that describes the figure and life of Mary Magdalene, stitched together from interpretations of New Testament figures, homilies, and apocrypha, was given a coherent visual identity in the visual and material culture of the Early Modern period, c.1400–1700. Linked to a catalogue of iconography that includes her hair, ointment jar, sumptuous garments, the landscape of her penitential retreat, books, and musical instruments, the saint was fitted to a reliable set of themes that reference these critical moments from her life: witness at the tomb, reveling in worldly luxuries, as a tearful penitent, and as a wilderness outcast. Early Modern depictions of Mary Magdalene are remarkable for their diversity and consistency, making her one of the most creatively and frequently visualized holy figures outside of the Virgin and Christ from the end of the Middle Ages through the Enlightenment.
Mary Magdalene in Christian Hymnody, Liturgical Music, and Drama
Authors: Loewen Peter V.
Published: June 2024

The various ways liturgists, dramatists, and song composers expound the details of Mary Magdalene’s life shows that her cult was a work in progress. Her identity was a source of considerable debate in the course of the Middle Ages. But when Pope Gregory the Great (c.540–604, r. 590–604) conflated Mary of Bethany, the sister of Lazarus and Martha, with of the women whom Jesus liberated of devils, and who anointed Jesus and wept at his feet and dried them with her hair, she became a complex, ardent, and a relatable personality. The church would go on to promulgate this conflated identity through its plainchants for Magdalene’s office. Taken together with the large repertory of medieval songs and dramas, Magdalene appears as a saintly avatar representing every human condition.
The specificities, influencing factors, and medical implications of bone circadian rhythms
Authors: Mei Gang , Wang Jinyu , Wang Jiajia , Ye Lanxiang , Yi Ming , Chen Guangjin , Zhang Yifan , Tang Qingming , Chen Lili
Published: June 2024

Physiological processes within the human body are regulated in approximately 24‐h cycles known as circadian rhythms, serving to adapt to environmental changes. Bone rhythms play pivotal roles in bone development, metabolism, mineralization, and remodeling processes. Bone rhythms exhibit cell specificity, and different cells in bone display various expressions of clock genes. Multiple environmental factors, including light, feeding, exercise, and temperature, affect bone diurnal rhythms through the sympathetic nervous system and various hormones. Disruptions in bone diurnal rhythms contribute to the onset of skeletal disorders such as osteoporosis, osteoarthritis and skeletal hypoplasia. Conversely, these bone diseases can be effectively treated when aimed at the circadian clock in bone cells, including the rhythmic expressions of clock genes and drug targets. In this review, we describe the unique circadian rhythms in physiological activities of various bone cells. Then we summarize the factors synchronizing the diurnal rhythms of bone with the underlying mechanisms. Based on the review, we aim to build an overall understanding of the diurnal rhythms in bone and summarize the new preventive and therapeutic strategies for bone disorders.
Heritable Thrombophilia and Increased Risk for Venous Thromboembolism Despite Thromboprophylaxis After Pelvis or Acetabulum Fracture
Authors: Shah Nihar S. , Pierrie Sarah N. , Agel Julie , Firoozabadi Reza , Sagi H. Claude
Published: June 2024

OBJECTIVES:

Individuals with pelvic and acetabular fractures are at high risk of venous thromboembolism (VTE). The purpose of this study was to determine whether serum markers for thrombophilia and rapid thromboelastography (r-TEG) values correlate with increased VTE risk among patients with pelvic and acetabular fractures.

METHODS:

.

Design:

Prospective observational study.

Setting:

Two urban academic level 1 trauma centers.

Patient Selection Criteria:

Adult patients with isolated pelvis and/or acetabulum fractures (OTA/AO 61 and 62) treated surgically placed on a standardized VTE chemoprophylaxis regimen with enoxaparin over a 5-year period were included.

Outcome Measures and Comparisons:

Serum r-TEG, coagulation laboratory values, and markers for heritable thrombophilia were drawn postoperatively and after completion of a 6-week course of enoxaparin. The primary outcome was VTE event (either deep venous thrombosis or pulmonary embolism) diagnosed using a Duplex ultrasound, chest computed tomography angiogram, or lung ventilation–perfusion ordered based on clinical suspicion of a VTE event. Laboratory markers and values were then compared between patients who went on to have a VTE event and those who did not and patients with and without markers of thrombophilia.

RESULTS:

One hundred thirty-three adult patients with isolated operative pelvic and/or acetabular fractures were enrolled in this study. The average age of patients at time of injury was 48.3 years (range 18–91). Sixty-seven percent of patients in the study were (n = 90) males. Sixty-three percent of patients (n = 84) completed both clinical and laboratory follow-up. Forty-one percent of patients (n = 54) had 1 or more markers of heritable thrombophilia. Twelve percent (n = 10) of patients who completed follow-up were diagnosed with VTE. Age, sex, and smoking status were not associated with VTE. Patients who developed VTE had a higher body mass index (P = 0.04). Having more than 1 marker of heritable thrombophilia (P = 0.004) and an r-TEG mean amplitude greater than 72 mm postoperatively was positively associated with VTE (P = 0.02).

CONCLUSIONS:

Among patients treated surgically for isolated pelvic and acetabular fractures who received enoxaparin prophylaxis, the presence of more than 1 marker of heritable thrombophilia or r-TEG mean amplitude value greater than 72 mm postoperatively was associated with an increased risk of VTE.

LEVEL OF EVIDENCE:

Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Scoliosis Development in Spinal Muscular Atrophy: The Influences of Genetic Severity, Functional Level, and Disease-Modifying Treatments
Authors: Ciftci Sadettin , Ulusaloglu Armagan C. , Shrader M. Wade , Scavina Mena T. , Mackenzie William G. , Heinle Robert , Neal Kevin M. , Stall Alec , Howard Jason J.
Published: June 2024

Background:

Spinal muscular atrophy (SMA) is caused by abnormalities of the survival motor neuron (SMN) 1 gene, leading to deficiency in SMN protein and loss of spinal cord alpha motor neurons. Newer disease-modifying agents (DMA) targeting the involved genes, including nusinersen and gene replacement therapies, have improved gross motor and respiratory function, but their impact on scoliosis development has not been established. This study aimed to determine risk factors for scoliosis development in SMA, specifically genetic severity and DMA use.

Methods:

In this retrospective cohort study, children with SMA and minimum 2-year follow-up were included. The primary outcome was the prevalence of clinically relevant scoliosis. Secondary outcomes included SMA type, SMN2 copy number, Hammersmith Functional Motor Scale (HFMS), ambulatory status [functional mobility scale at 50m (FMS50)], DMA use, and hip displacement as risk factors. Univariate/multivariate logistic regression analyses were performed to identify dependent/independent risk factors.

Results:

One hundred sixty-five patients (51% female) with SMA types I-III met the inclusion criteria, with total follow-up of 9.8 years. The prevalence of scoliosis was 79%; age of onset 7.9 years. The major curve angle for the entire cohort at first assessment and final follow-up was 37 degrees (SD: 27 degrees) and 62 degrees (SD: 31 degrees) (P<0.0001), respectively. Significant risk factors for scoliosis by univariate analysis were SMA type (I/II, P=0.02), HFMS (>23, P<0.001), nonambulatory status (FMS50=1, P<0.0001), DMA treatment (P=0.02), and hip displacement (P<0.0001). Multivariate analysis revealed that HFMS >23 (P=0.02) and DMA (P=0.05) treatment were independent (protective) risk factors.

Conclusions:

The development of scoliosis in SMA is high, with risk factors associated with proxy measures of disease severity, including SMA type, nonambulatory status, hip displacement, and most notably, gross motor function (by HFMS). DMA use and HFMS >23 were associated with a decreased risk of scoliosis development. Identified risk factors can be used in the development of surveillance programs for early detection of scoliosis in SMA.

Level of Evidence:

Level III.
A contemporary step-by-step guide to performing flexible ureterorenoscopy for renal calculi
Authors: Fonseka Thomas , Melchionna Alberto , De Luyk Nicolo , Arumuham Vimoshan , Choong Simon
Published: June 2024

With advancements in laser technology and urological techniques, flexible ureterorenoscopy has emerged as a vital surgical approach for managing stone disease. Various techniques can be employed to customize endourological stone treatments. Despite the continuous evolution of equipment, it remains crucial to comprehend the fundamental steps of the procedure. This paper offers a comprehensive step-by-step guide that integrates the latest advancements in both scopes and lasers. Additionally, it outlines potential pitfalls and strategies to circumvent them, aiming to achieve optimal stone clearance and deliver individualized patient care safely and efficiently.
Adolescent predictors of young adult pain and health outcomes: results from a 6-year prospective follow-up study
Authors: Murray Caitlin B. , Li Rui , Kashikar-Zuck Susmita , Zhou Chuan , Palermo Tonya M.
Published: June 2024

Adolescent chronic pain may lead to persistent disability and long-term health impairments in adulthood. However, our understanding of which youth are more likely to experience adverse outcomes remains limited. To address this gap, this longitudinal cohort study examined adolescent predictors of various dimensions of young adult health and functioning, including pain, physical health, depression, anxiety, social isolation, and sleep disturbance. As part of a previous clinical trial, we recruited a cohort of adolescents (ages 11-17 years, M age = 14 years) with non–disease-related chronic pain from 15 tertiary pain clinics in North America. Approximately 6 years later, 229 of the original 273 individuals (81% participation rate) completed a follow-up survey as young adults (ages 18-25 years, M age = 21 years). At the young adult follow-up, 73% reported continued chronic pain, with two-thirds experiencing moderate-to-severe pain interference. Youth reported several adverse health outcomes, including below-average physical health (37%), clinically elevated depression (42%), clinically elevated anxiety (48%), and sleep disturbances (77%). Multivariate regression analyses controlling for sociodemographic characteristics revealed that higher pain intensity, more pain locations, lower sleep quality, and greater anxiety symptoms in adolescence predicted worse pain outcomes in young adulthood. Moreover, lower sleep quality, greater anxiety symptoms, and worse family functioning predicted worse physical and psychosocial health in adulthood. These findings represent an important first step toward identifying ways to optimize psychological pain interventions. Tailored psychological pain interventions can directly target adolescent vulnerabilities, including mood, sleep, and family risk factors, with the potential to disrupt a lifelong trajectory of pain and suffering.
The polymorphism Val158Met in the COMT gene: disrupted dopamine system in fibromyalgia patients?
Authors: Gerra Maria Carla , Dallabona Cristina , Manfredini Matteo , Giordano Rocco , Capriotti Camilla , González-Villar Alberto , Triñanes Yolanda , Arendt-Nielsen Lars , Carrillo-de-la-Peña Maria Teresa
Published: June 2024

The single-nucleotide polymorphism (SNP) rs4680 in the catechol-O-methyltransferase gene (COMT) is a missense variant (Val158Met) associated with altered activity of the COMT enzyme and suggested as a predictive feature for developing some chronic pain conditions. However, there are controversial results on its role in fibromyalgia (FM). Here, the SNP Val158Met was analyzed in 294 FM patients (without comorbidities) and 209 healthy controls (without chronic pain). The concurrent impact of Val158Met genotypes and FM comorbid disorders (depression and sleep impairment) on FM risk were tested. In addition, the genotypic distribution of FM patients in relation to pain intensity was evaluated. The G allele (Val) resulted in being more represented in the FM group (57.8%) compared with the control group (48.8%; P = 0.037). Logistic regression highlighted that having the G/G (Val/Val) homozygous genotype was associated with 2 times higher risk of having FM compared with the A/A (Met/Met) carriers (P = 0.038), whereas depression and sleep impairment increased FM risk by 12 and 8 times, respectively (P < 0.001). However, considering only the FM patient group, the A/A homozygous genotype was significantly associated with severe pain intensity (P = 0.007). This study highlighted associations between the SNP Val158Met and both FM and pain intensity, suggesting a link between dopaminergic dysfunction and vulnerability to chronic pain. Further studies should explore this SNP in FM patients in conjunction with COMT enzymatic activity and other symptoms connected with the dopaminergic system such as depression or sleep impairment.
Modified traditional TNM staging of pyriform sinus and hypopharyngeal and laryngeal cancer based on lymph node ratio and its clinical significance: a population-based study combined with external validation
Authors: Yue Jing , Cai Hang , Zhang Guangxin , Wei Xianping , Jin Yue , Sun Yang , Liu Xueshibojie
Published: June 2024

Background:

To evaluate the application value of a new tumor–node–metastasis lymph node ratio-modified (TLNRM) staging prediction model based on lymph node ratio (LNR) in patients with pyriform sinus and hypopharyngeal and laryngeal cancer (PHLC).

Materials and methods:

A total of 2257 patients with pathologically diagnosed PHLC from 2004 through 2019 were collected from the SEER database for analysis. The N staging of AJCC was replaced by LNR, and we compared the differences in patient prognosis and judgment ability between the new TLNRM staging and the 8th edition TNM staging. At the same time, data from 1094 people in our hospital were included for external verification and validation.

Results:

We selected four cutoff points based on LNR and reclassified N staging into five groups (LNR1–5). Compared to the traditional TNM staging (8th edition), the new TLNRM staging showed a statistically significant 5-year overall survival difference. The decision curve showed that the new TLNRM staging had a higher net benefit for different decision thresholds than the traditional TNM staging system’s prediction line. The smaller Akaike information criterion (AIC) and Bayesian information criterion (BIC) suggested that the new staging system had a higher sensitivity to prognosis evaluation compared to the traditional staging system. TLNRM stage III patients can benefit from radiotherapy, while TLNRM IVA and IVB patients can benefit from chemoradiotherapy. The same conclusion has been drawn from external validation data from our center.

Conclusions:

Compared with the traditional 8th edition AJCC staging system, the new TLNRM staging system has advantages in predicting the staging and prognosis of PHLC patients and can independently guide postoperative chemoradiotherapy in patients.
Gastroenterology healthcare in LGBTQ+ individuals
Authors: Coelho Rosa , Gonçalves Raquel , Mendes Francisco , Macedo Guilherme
Published: June 2024

Lesbian, gay, bisexual, transgender, queer, or questioning individuals, as well as those with another diverse identity (LGBTQ+), present specific nuances in healthcare that physicians must consider in clinical practice. Particularly, gastroenterologists are nowadays facing different issues in several fields regarding LGBTQ+ healthcare, such as endoscopy, inflammatory bowel disease, hepatology, and proctology. In this study, the authors provide a practice-oriented and up-to-date review reinforcing the importance of some of the most prevalent pathologies associated with sexuality that gastroenterologists may encounter in their clinical practice. In terms of endoscopy, authors describe the endoscopic findings related to human papillomavirus (HPV) infection: the esophageal squamous papilloma and cell carcinoma; also highlight the importance of retroflexion maneuver during a routine colonoscopy that allows detection of anal intraepithelial neoplasia lesions that can be anal cancer precursors. Regarding inflammatory bowel disease, some considerations are made about the differential diagnosis with infectious proctitis, and the topic of the risk of anal cancer due to HPV infection, in this specific population, is also addressed. Considering hepatology, the authors review the most important issues related to hepatotropic sexually transmitted infections. The authors also make some comments regarding the possibility of drug-induced liver injury in gender-affirming hormone therapy and pre-exposure prophylaxis for HIV prevention. Finally, considering the proctology field, an up-to-date review is performed regarding anal cancer screening, HPV infection and related diseases, and infectious proctitis management.
Effectiveness of facilitated tucking on reducing pain during heel stick in neonates: a randomized controlled experimental study
Authors: Subedi Rejeena , Bhatta Mukesh , Chaudhary Ramananda , Karn Basant K. , Yadav Upendra , Yadav Shankar P.
Published: June 2024

Background:

Pain in neonates is associated with adverse neurodevelopmental outcomes in the later days of life. Facilitated tucking is a nonpharmacological method of pain relief. The study aims to compare the effect of facilitated tucking in pain reduction in neonates.

Materials and methods:

This was a randomized controlled experimental study conducted in the neonatal ward of a tertiary care center. There were 25 neonates randomized each in the experimental and control groups (total of 50), based on computer-generated random tables. The experimental group was placed in a facilitated tucking position during heel stick, while the control group was kept in the usual position, as done routinely. A self-structured questionnaire and Neonatal Infant Pain Scale were used. The main outcome measures were the mean Neonatal Infant Pain Scale score, and change in preprocedure and postprocedure heart rate and oxygen saturation in the two groups. Ethical clearance and informed written consent were sought.

Results:

Neonates in the experimental group had significantly lesser pain (less Neonatal Infant Pain Scale score) than the neonates in the control group (P<0.001). There was also a significant increment in the mean heart rate and a decrease in the oxygen saturation after the procedure in the control group, indicating significantly more pain perception (P<0.001) in the control group.

Conclusions:

Facilitated tucking was found to be effective in reducing the pain during heel stick procedures in neonates.
MEIBO (perfluorohexyloctane): a novel approach to treating dry eye disease
Authors: Azhar Ayesha , Taimuri Muskan A. , Oduoye Malik Olatunde , Sumbal Anusha , Sheikh Ayesha , Iqbal Amna , Ikram Areeba , Waqar Eisha
Published: June 2024

Dry eye disease (DED) or keratoconjunctivitis sicca (KCS) is a multifactorial disease that classically develops due to the hyperosmolarity of the tear film. Categorically divided into two types, based on decreased production and increased evaporation of the tear film, DED begins with a spectrum of nonspecific symptoms like pruritus, redness, burning and discomfort, progressively leading to stringy mucus eye discharge, photophobia, twitching, visual fluctuations, and punctate epithelial lesions. This disease has numerous treatment options, including medications, artificial tear inducers, and surgical manoeuvres that prevent water loss from the tear film. However, each of these treatment options has its limitations. The Food and Drug Administration (FDA) has approved another intervention, Meibo (perfluorohexyloctane), as a choice of management for dry eye disease. With its shielding action on the ocular surface, Meibo (perfluorohexyloctane) reduces desiccation stress-induced ocular damage, making it highly specific for treating DED. Available in an eye drop formulation of perfluorohexyloctane (PFHO), these drops can reduce saline evaporation by up to 80%. The methods we used for this analysis are literature searches from PubMed, Medline and Google Scholar. This study aims to scour varying differentials of DED, its aetiology, general interventions, the latest refinements, and clinical efficacy, safety, and trials associated with Meibo (perfluorohexyloctane) in the management of DED.
The Prognostic Value of Tumor Cell Clusters in the Fallopian Tube Lumen in Stage I Endometrioid Carcinoma
Authors: Yoo Ye Jin , Kim Yeon Joo , Kim Yong-Man , Kim Kyu-Rae , Jo Uiree , Kim Young Seok
Published: June 2024

The aim of this study was to investigate the pathologic prognostic factors such as tumor cell clusters (TCCs) in the fallopian tube lumen, myometrial invasion patterns, and positive peritoneal cytology (PPC) in women with Stage I endometrial endometrioid carcinoma (EEC). From 2009 to 2020, consecutive patients with Stage I EEC who underwent hysterectomy and bilateral salpingectomy were included. The primary outcome was the recurrence-free survival (RFS) rate, and the clinicopathological factors affecting RFS were analyzed. A total of 765 patients were enrolled. Seventeen patients (2.2%) had TCC in the fallopian tube lumen, and 58 patients showed a microcystic elongated and fragmented pattern (7.6%). PPC was found in 19 patients (2.5%). The median follow-up period was 61.0 months (range: 2.0–149.7). The majority (88.6%) of patients had Stage IA EEC. The 5-year RFS and overall survival rates were 97.5% and 98.5%, respectively. In multivariate analysis for RFS, the significant prognostic factors were lymphovascular invasion (hazard ratio = 4.604; 95% CI: 1.387–15.288; P = 0.013) and grade (grade 2; hazard ratio = 4.949; 95% CI: 1.035–23.654; P = 0.045, and grade 3; hazard ratio = 5.469; 95% CI: 1.435–20.848; P = 0.013). Other pathologic factors including TCC in the fallopian tube lumen, myometrial invasion patterns, PPC, and hormonal status had no prognostic significance. TCC in the fallopian tube lumen, myometrial invasion pattern, PPC, and estrogen and progesterone receptor positivity were not significant prognostic factors in Stage I EEC. In contrast, lymphovascular invasion and grade were significant prognostic factors.
Associations of Sleep Deficiency With Sexual Risk Behaviors and HIV Treatment Outcomes Among Men Who Have Sex With Men Living With or at High Risk of Acquiring HIV
Authors: Rosen Allison D. , Javanbakht Marjan , Shoptaw Steven J. , Seamans Marissa J. , Gorbach Pamina M.
Published: June 2024

Background:

Associations of sleep deficiency and methamphetamine use with sexual health and HIV treatment outcomes are poorly understood.

Setting:

A longitudinal cohort of men who have sex with men at risk for or living with HIV (the mSTUDY) was analyzed. This analysis included 1445 study visits among 382 participants. Data were collected from June 2018 to February 2022.

Methods:

Semiannual study visits included self-interviews for sleep deficiency, sexual behaviors, substance use, and HIV treatment. Sleep deficiency was measured using the Pittsburgh Sleep Quality Index. Participants provided specimens for HIV viral load and sexually transmitted infection (STI) testing (chlamydia, gonorrhea, syphilis). Associations between sleep deficiency and STI/HIV outcomes were estimated using multiple logistic regression.

Results:

Across visits, the prevalence of sleep deficiency was 56%, with 33% reporting methamphetamine use and 55% living with HIV. Sleep deficiency was associated with reporting at least 1 new anal sex partner (aOR = 1.62, 95% CI: 1.21 to 2.15), exchange sex (aOR = 2.71, 95% CI: 1.15 to 6.39), sex party attendance (aOR = 2.60, 95% CI: 1.68 to 4.04), and missing HIV medications (aOR = 1.91, 95% CI: 1.16 to 3.14). The association between sleep deficiency and exchange sex differed for participants who did and did not report the use of methamphetamine (P = 0.09).

Conclusion:

Sleep deficiency was associated with sexual health and HIV treatment behaviors after accounting for methamphetamine use. Sleep health should be considered in STI/HIV prevention, particularly for those who use methamphetamine.
Layered Composite Dorsal Onlay Implant for Augmentation Rhinoplasty
Authors: Wu Lehao , You Jianjun , Xu Yihao , Tian Le , Zhang Xulong , Wang Huan
Published: June 2024

The use of autologous costal cartilage in augmentation rhinoplasty is well-established. However, scenarios where costal cartilage is insufficient or patients are unwilling to undergo additional cartilage harvesting present a challenge. This study introduces a composite dorsal onlay implant, combining silicone and costal cartilage, as an effective solution. Twenty female patients were enrolled in this study. Of these patients, 8 underwent revision surgery who had previous rhinoplasty with costal cartilage graft, and 12 had never previously undergone surgery involving the harvesting of costal cartilage. The implant, created by suturing a silicone base with a costal cartilage overlay, demonstrated low rates of warping and translucency over a mean follow-up of 11.4 months. This method offers a refined nasal appearance, particularly a higher dorsum with reduced translucency for patients with limited costal cartilage availability.
The Use and Impact of a Decision Support Tool for Appendicitis Treatment
Authors:   The TRIAD Collaborative,, Rosen Joshua E. , Monsell Sarah E. , DePaoli Sara C. , Fannon Erin C. , Kohler Johnathan E. , Reinke Caroline E. , Kao Lillian S. , Fransman Ryan B. , Stulberg Jonah J. , Shapiro Michael B. , Nehra Deepika , Park Pauline K. , Sanchez Sabrina E. , Fischkoff Katherine N. , Davidson Giana H. , Flum David R.
Published: June 2024

Objective:

Since introducing new and alternative treatment options may increase decisional conflict, we aimed to describe the use of the decision support tool (DST) and its impact on treatment preference and decisional conflict.

Background:

For the treatment of appendicitis, antibiotics are an effective alternative to appendectomy, with both approaches associated with a different set of risks (eg, recurrence vs surgical complications) and benefits (eg, more rapid return to work vs decreased chance of readmission). Patients often have limited knowledge of these treatment options, and DSTs that include video-based educational materials and questions to elicit patient preferences about outcomes may be helpful. Concurrent with the Comparing Outcomes of Drugs and Appendectomy trials, our group developed a DST for appendicitis treatment (www.appyornot.org).

Methods:

A retrospective cohort including people who self-reported current appendicitis and used the AppyOrNot DST between 2021 and 2023. Treatment preferences before and after the use of the DST, demographic information, and Ottawa Decisional Conflict Scale (DCS) were reported after completing the DST.

Results:

A total of 8243 people from 66 countries and all 50 U.S. states accessed the DST. Before the DST, 14% had a strong preference for antibiotics and 31% for appendectomy, with 55% undecided. After using the DST, the proportion in the undecided category decreased to 49% (P < 0.0001). Of those who completed the Ottawa Decisional Conflict Score (DCS; n = 356), 52% reported the lowest level of decisional conflict (<25) after using the DST; 43% had a DCS score of 25 to 50, 5.1% had a DCS score of >50 and 2.5% had and DCS score of >75.

Conclusions:

The publicly available DST appyornot.org reduced the proportion that was undecided about which treatment they favored and had a modest influence on those with strong treatment preferences. Decisional conflict was not common after use. The use of this DST is now a component of a nationwide implementation program aimed at improving the way surgeons share information about appendicitis treatment options. If its use can be successfully implemented, this may be a model for improving communication about treatment for patients experiencing emergency health conditions.
Issues in Distinguishing Sex and Gender in Surgical Registries: NSQIP and VASQIP Analysis
Authors: Jacobs Michael A , Eckstrand Kristen L , Gero J Joy , Blosnich John R , Hall Daniel E
Published: June 2024

BACKGROUND:

Surgical registries do not have separate sex (the biological construct) and gender identity variables. We examined procedures specific to sexually dimorphic anatomy, such as ovaries, testes, and other reproductive organs, to identify “discrepancies” between recorded sex and the anatomy of a procedure. These “discrepancies” would represent a structural limitation of surgical registries, one that may unintentionally perpetuate health inequities.

STUDY DESIGN:

This was a retrospective cohort study using NSQIP from 2015 to 2019 and Veterans Affairs Surgical Quality Improvement Program (VASQIP) from 2016 to 2019. Surgeries were limited to procedures pertaining to anatomy that is either specifically male (CPT codes 54000 to 55899) or female (56405 to 59899). The sex recorded in the surgical registries, often automatically retrieved from electronic health record data, was compared with the specified anatomy of each procedure to quantify discrepancies.

RESULTS:

A total of 575,956 procedures were identified specific to sexually dimorphic anatomy (549,411 NSQIP and 26,545 VASQIP). Of those, 2,137 recorded a sex discordant with the anatomy specified by the surgical procedure (rates 0.4% in NSQIP and 0.2% in VASQIP). Procedures specific to female anatomy with recorded male sex were more frequent (82.6% in NSQIP and 98.4% in VASQIP) than procedures specific to male anatomy with recorded female sex.

CONCLUSIONS:

Discrepancies between recorded sex and the anatomy of a surgical procedure were limited. However, because sex in surgical registries is often directly acquired from electronic health record data, these cases likely represent transgender, gender diverse, or living with a difference of sex development (intersex) patients. As these populations increase and continue to seek healthcare, precise measurement of sex, gender identity, and legal sex is necessary for adequate risk adjustment, risk prediction, and surgical outcomes benchmarking for optimal care.
We must discuss research environments
Authors: Gallacher John , Webster Chris
Published: June 2024

A major challenge facing the biomedical community is creating and sustaining high-quality research environments. A literature search identified five common themes underlying biomedical research environments comprising collaboration, data access, user-led innovation, data provenance and a deep commitment to public and scientific benefit. Club theory is used to develop a model describing social structures that underpin these themes. It is argued that collaboration underlies impactful science and that collaboration is hindered by high transaction costs. This, combined with poorly defined property rights surrounding publicly funded data, limits the ability of data markets to operate efficiently. Although the science community is best placed to provide solutions for these issues, incentivization by funding agencies to increase the benefits of collaboration and reduce uncoordinated activity will be an accelerator. Given the complexity of emerging datasets and the collaborations needed to exploit them, trust-by-design solutions are suggested. The underlying motivational ‘glue’ that holds this activity together is the aesthetic and ethical value base underlying good science. The model has implications for data-driven science more generally. As biomedical science in the Global South develops, there is an opportunity to address foundational structural issues prospectively rather than inherit unwanted constraints of current practice.
A genetic algorithm optimization framework for the characterization of hyper-viscoelastic materials: application to human articular cartilage
Authors: Allen Piers , Cox Sophie C. , Jones Simon , Espino Daniel M.
Published: June 2024

This study aims to develop an automated framework for the characterization of materials which are both hyper-elastic and viscoelastic. This has been evaluated using human articular cartilage (AC). AC (26 tissue samples from 5 femoral heads) underwent dynamic mechanical analysis with a frequency sweep from 1 to 90 Hz. The conversion from a frequency- to time-domain hyper-viscoelastic material model was approximated using a modular framework design where finite element analysis was automated, and a genetic algorithm and interior point technique were employed to solve and optimize the material approximations. Three orders of approximation for the Prony series were evaluated at
N
= 1, 3 and 5 for 20 and 50 iterations of a genetic cycle. This was repeated for 30 simulations of six combinations of the above all with randomly generated initialization points. There was a difference between
N
= 1 and
N
= 3/5 of approximately ~5% in terms of the error estimated. During unloading the opposite was seen with a 10% error difference between
N
= 5 and 1. A reduction of ~1% parameter error was found when the number of generations increased from 20 to 50. In conclusion, the framework has proved effective in characterizing human AC.
Evolutionary rescue in resistance to pesticides
Authors: Madgwick Philip G. , Tunstall Thomas , Kanitz Ricardo
Published: June 2024

Evolutionary rescue occurs when the genetic evolution of adaptation saves a population from decline or extinction after environmental change. The evolution of resistance to pesticides is a special scenario of abrupt environmental change, where rescue occurs under (very) strong selection for one or a few de novo resistance mutations of large effect. Here, a population genetic model of evolutionary rescue with density-dependent population change is developed, with a focus on deriving results that are important to resistance management. Massive stochastic simulations are used to generate observations, which are accurately predicted using analytical approximations. Key results include the probability density function for the time to resistance and the probability of population extinction. The distribution of resistance times shows a lag period, a narrow peak and a long tail. Surprisingly, the mean time to resistance can increase with the strength of selection because, if a mutation does not occur early on, then its emergence is delayed by the pesticide reducing the population size. The probability of population extinction shows a sharp transition, in that when extinction is possible, it is also highly likely. Consequently, population suppression and (local) eradication can be theoretically achievable goals, as novel strategies to delay resistance evolution.
Benchmarking short-, long- and hybrid-read assemblers for metagenome sequencing of complex microbial communities
Authors: Goussarov Gleb , Mysara Mohamed , Cleenwerck Ilse , Claesen Jürgen , Leys Natalie , Vandamme Peter , Van Houdt Rob
Published: June 2024

Metagenome community analyses, driven by the continued development in sequencing technology, is rapidly providing insights in many aspects of microbiology and becoming a cornerstone tool. Illumina, Oxford Nanopore Technologies (ONT) and Pacific Biosciences (PacBio) are the leading technologies, each with their own advantages and drawbacks. Illumina provides accurate reads at a low cost, but their length is too short to close bacterial genomes. Long reads overcome this limitation, but these technologies produce reads with lower accuracy (ONT) or with lower throughput (PacBio high-fidelity reads). In a critical first analysis step, reads are assembled to reconstruct genomes or individual genes within the community. However, to date, the performance of existing assemblers has never been challenged with a complex mock metagenome. Here, we evaluate the performance of current assemblers that use short, long or both read types on a complex mock metagenome consisting of 227 bacterial strains with varying degrees of relatedness. We show that many of the current assemblers are not suited to handle such a complex metagenome. In addition, hybrid assemblies do not fulfil their potential. We conclude that ONT reads assembled with CANU and Illumina reads assembled with SPAdes offer the best value for reconstructing genomes and individual genes of complex metagenomes, respectively.
An RNA interference approach for functional studies in the sea urchin and its use in analysis of Nodal signaling gradients
Authors: Wilson Keen , Manner Carl , Miranda Esther , Berrio Alejandro , Wray Gregory A , McClay David R
Published: June 2024

Dicer substrate interfering RNAs (DsiRNAs) destroy targeted transcripts using the RNA-Induced Silencing Complex (RISC) through a process called RNA interference (RNAi). This process is ubiquitous among eukaryotes. Here we report the utility of DsiRNA in embryos of the sea urchinLytechinus variagatus (Lv).Specific knockdowns phenocopy known morpholino and inhibitor knockdowns, and DsiRNA offers a useful alternative to morpholinos. Methods for designing and obtaining specific DsiRNAs that lead to destruction of targeted mRNA are described. DsiRNAs directed againstpks1, an enzyme necessary for pigment production, show how successful DsiRNA perturbations are monitored by RNAin situanalysis and by qPCR to determine relative destruction of targeted mRNA. DsiRNA-based knockdowns phenocopy morpholino- and drug-based inhibition ofnodalandlefty. Other knockdowns demonstrate that the RISC operates early in development as well as on genes that are first transcribed hours after gastrulation is completed. Thus, DsiRNAs effectively mediate destruction of targeted mRNA in the sea urchin embryo. The approach offers significant advantages over other widely used methods in the urchin in terms of cost, and ease of procurement, and offers sizeable experimental advantages in terms of ease of handling, injection, and knockdown validation.

Highlights

DsiRNA provides an RNAi approach for perturbation of sea urchin embryos. A dilution series of DsiRNA oligos reveals properties of the Nodal gradient in establishing the Dorsal-Ventral axis.
Decorin enhances metabolic maturation by activating AMPK-PGC1A pathway in cardiac organoids
Authors: Song Myeong-Hwa , Jun Seongmin , Choi Seung-Cheol , Na Ji Eun , Rhyu Im Joo , Hwang Sun Wook , Jeon Minji , Lim Do-Sun
Published: June 2024

Rationale

Cardiac organoids (COs) are advanced models for investigating heart development and disease, while require maturation to resemble the structural and functional characteristics of the human heart.

Objective

This study reveals the role of Decorin (DCN) contributes to the mature and vascularized COs and assesses the biological mechanism responsible for CO maturation.

Methods and Results

DCN-treated COs exhibit structural maturation involving aligned sarcomere, mitochondria, and t-tubule structures, and vessel formations, as well as functional maturation involving synchronized contraction-relaxation, Ca2+ transient, and increases ion channel expressions. DCN-treated COs also show metabolic maturation, including enhanced fatty acid oxidation and increased mitophagy. Transcriptional profiling results indicate that DCN-treated COs have increased levels of AMPK signaling and mitophagy. In DCN-treated COs, AMPK knockdown affects mitochondrial biogenesis, cardiac metabolism, ion channels, and mitophagy.

Conclusions

These findings indicate that DCN is crucial for development of mature, vascularized COs and that CO maturation is primarily regulated through AMPK signaling, which is triggered by DCN.

Abstract Figure

GRAPHIC ABSTRACT

A graphic abstract is available for this article.

DCN enhances metabolic maturation in COs by AMPK-triggered regulation of the glycolysis, fatty acid oxidation, and mitophagy.
α/β-Hydrolase domain-containing 6 (ABHD6) accelerates the desensitization and deactivation of TARP γ-2-containing AMPA receptors
Authors: Cong Rixu , Li Huiran , Yang Hong , Gu Jing , Wang Shanshan , Guan Xiangyu , Su Tangyunfei , Zheng Yunlin , Wang Dianchun , Chen Xinran , Yang Lei , Shi Yun Stone , Wei Mengping , Zhang Chen
Published: June 2024

AMPA receptors (AMPARs) mediate most of the fast excitatory synaptic transmission in mammalian brain. Their efficacy in responding to presynaptic glutamate release depends on their kinetics, which are determined by AMPARs and their auxiliary subunit composition. α/β-Hydrolase domain-containing 6 (ABHD6) is an AMPAR auxiliary subunit that has been shown to negatively regulate the surface delivery of AMPARs and AMPAR-mediated currents. Overexpression of ABHD6 decreased the rising slope and increased the decay τ of mEPSCs. However, whether ABHD6 is involved in regulating AMPAR kinetics remains unclear. Here, we found that ABHD6 per se had no effects on the gating kinetics of GluA1 and GluA2(Q) containing homomeric receptors. However, in the presence of the auxiliary subunit TARP γ-2, ABHD6 accelerated the deactivation and desensitization of either GluA1 and GluA2(Q) containing homomeric receptors independent of their splicing isoforms (flip and flop) and the editing isoforms of GluA2 (R or G at position 764), except the deactivation of GluA2(Q)i-G isoform. Besides, the recovery from desensitization of GluA1 with flip splicing isoform was slowed by the co-expression of ABHD6 in the presence of TARP γ-2. Furthermore, the ABHD6 accelerated the deactivation and desensitization of GluA1i/GluA2(R)i-G heteromeric receptors in the presence of TARP γ-2. Therefore, these results demonstrate that ABHD6 regulates AMPAR gating kinetics in a TARP γ-2-dependent manner.

SIGNIFICANCE STATEMENT

The efficacy of AMPARs in responding to presynaptic glutamate release depends on their kinetics, including deactivation, desensitization, and recovery from desensitization, which are determined by AMPARs and their auxiliary subunit composition. Using ultra-fast application of glutamate and outside-out patch recordings, we found that, in the presence of the auxiliary subunit TARP γ-2, ABHD6 accelerated the deactivation and desensitization of GluA1i/GluA2(R)i-G heteromeric receptors and GluA1 and GluA2(Q) containing homomeric receptors independent of their splicing isoforms (flip and flop) and the editing isoforms of GluA2 (R or G at position 764), except the deactivation of GluA2(Q)i-G isoform. These results demonstrate that ABHD6 regulates AMPAR gating kinetics in a TARP γ-2-dependent manner.
Improving positively tuned voltage indicators for brightness and kinetics
Authors: Lee Sungmoo , Zhang Guofeng , Gomez Laura C. , Testa-Silva Guilherme , Hao Yukun Alex , Hiramoto Atsuki , Jiang Dongyun , Roth Richard H. , Ding Jun , Clandinin Thomas R. , Roska Botond , Feldman Daniel , Ji Na , Lin Michael Z.
Published: June 2024

The recent positively tuned ASAP4-family voltage indicators feature superior photostability compared to the negatively tuned ASAP3, but signal-to-noise ratios (SNRs) for spike detection were not significantly different. To improve spike detection by positively tuned ASAP indicators, we performed multiple rounds of structure-guided saturation mutagenesis of an ASAP4 template while screening directly for faster responses. Our resulting variants, ASAP6.1 and ASAP6b, demonstrated sufficient dynamic range and kinetics, and reported action potentialsin vivoby one-photon and two-photon microscopy with high SNR and temporal resolution.

Previously, we developed positively tuned ASAP4-subfamily GEVIs with high photostability1. While these had higher ΔF/F0from –70 mV to +30 mV than the negatively tuned ASAP32or ASAP5, their F-V curves were spread out over a larger voltage range. In addition, ASAP4b and ASAP4e onset kinetics are biexponential with only a minority component of the response exhibiting a time constant of < 10 ms. Both limitations could be due to steric or electrostatic interactions that cause resistance to upward S4 movement in ASAP4 variants. Thus, we set out to engineer positively tuned GEVIs with faster activation kinetics over ASAP4b and ASAP4e, while maintaining or improving steady-state responsivity.