bluuebunny/crossref_metadata_2025 huggingface dataset:
Pathways and Referral of Patients with Cancer in Rural Ethiopia: A Multi-center Retrospective Cohort Study
Authors: Trabitzsch Josephin , Wondimagegnehu Abigiya , Afework Tsion , Stoeter Ole , Gizaw Muluken , Getachew Sefonias , Feyisa Jilcha Diribi , Taylor Lesley , Wienke Andreas , Addissie Adamu , Kantelhardt Eva Johanna
Published: March 2023

Introduction

Well-organized patient pathways are essential to achieve early diagnosis and timely treatment of patients with cancer in Sub-Saharan Africa. This retrospective cohort study describes pathways and referral patterns of cancer patients in rural Ethiopia.

Patients and Methods

The retrospective study took place from October to December 2020 at 2 primary- and 6 secondary-level hospitals in southwestern Ethiopia. Of 681 eligible patients diagnosed with cancer between July 2017 and June 2020, 365 patients were included. Structured interviews on the patients’ pathways were conducted by telephone. The primary outcome was successful referral, which was defined as occurring when the intended procedure was initiated at the receiving institution. Logistic regression was used to assess factors associated with successful referrals.

Results

Patients visited on average 3 health care institutions from their first encounter with a provider until their final treatment initiation. After diagnosis, only 26% (95) of patients were referred for further cancer treatment, of which 73% were successful. Patients referred for diagnostic tests were 10 times more likely to complete referrals successfully than patients referred for treatment. Overall, 21% of all patients remained without any therapy.

Conclusion

We found that referral pathways of patients with cancer in rural Ethiopia were largely cohesive. The majority of patients referred for diagnostic or treatment services followed the advice. Nevertheless, an unacceptable number of patients remained without any treatment. Capacity for cancer diagnosis and treatment at primary- and secondary-level health facilities in rural Ethiopia must be expanded to enable early detection and timely care.
Can Central Banks Boost Corporate Investment? Evidence from ECB Liquidity Injections
Authors: von Rüden Stine Louise , Subrahmanyam Marti G , Tang Dragon Yongjun , Wang Sarah Qian
Published: March 2023

Liquidity injections by central banks have become frequent and massive, but their real effects on corporate investment remain unclear. We examine the longer-term refinancing operations (LTROs) of the European Central Bank (ECB) during the eurozone sovereign crisis and show that greater LTRO funding to banks is associated with lower corporate investment. Riskier banks received funds through the LTROs and subsequently increased their holdings of risky sovereign debt. Corporate investment reductions are associated with these banks. Further, concurrent fiscal and regulatory policies impeded the effectiveness of the ECB liquidity injections. Our findings identify the contributing factors for these failures of monetary policy. (JEL E52, E58, G32)

Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
Self-reported Gesture Interpretation and Performance Deficits in Individuals at Clinical High Risk for Psychosis
Authors: Karp Erica L , Williams Trevor F , Ellman Lauren M , Strauss Gregory P , Walker Elaine F , Corlett Philip R , Woods Scott W , Powers Albert R , Gold James M , Schiffman Jason E , Waltz James A , Silverstein Steven M , Mittal Vijay A
Published: March 2023

Background and hypothesis

Deficits in performing and interpreting communicative nonverbal behaviors, such as gesture, have been linked to varied psychopathology and dysfunction. Some evidence suggests that individuals at risk for psychosis have deficits in gesture interpretation and performance; however, individuals with internalizing disorders (eg, depression) may have similar deficits. No previous studies have examined whether gesture deficits in performance and interpretation are specific to those at risk for psychosis. Additionally, the underlying mechanisms (eg, cognition) and consequences (eg, functioning) of these deficits are poorly understood.

Study design

This study examined self-reported gesture interpretation (SRGI) and performance (SRGP) in those at clinical high risk for psychosis (CHR; N = 88), those with internalizing disorders (INT; N = 51), and healthy controls (HC; N = 53). Participants completed questionnaires, clinical interviews, and neurocognitive tasks.

Study results

Results indicated that the CHR group was characterized by significantly lower SRGI scores than the HC or INT groups (d = 0.41); there were no differences among groups in SRGP. Within CHR participants, greater deficits in SRGP were associated with lower verbal learning and memory (r = −.33), but not general intelligence or processing speed. Furthermore, gesture deficits were associated with higher cross-sectional risk for conversion to a full psychotic disorder in the CHR group.

Conclusions

Overall, these findings suggest that specific subdomains of gesture may reflect unique vulnerability for psychosis, self-report may be a viable assessment tool in understanding these phenomena, and gesture dysfunction may signal risk for transition to psychosis.
Predisposition to soil-transmitted helminth reinfection after four rounds of mass drug administration: results from a longitudinal cohort in the Geshiyaro project, a transmission elimination feasibility study in the Wolaita zone of southern Ethiopia
Authors: Rayment Gomez Santiago , Maddren Rosie , Liyew Ewnetu Firdawek , Chernet Melkie , Anjulo Ufaysa , Tamiru Adugna , Mengitsu Birhan , Forbes Kathryn , Collyer Benjamin , Salasibew Mihretab , Anderson Roy
Published: March 2023

Background

Current WHO strategies for reaching soil-transmitted helminths (STH) elimination as a public health problem excludes treating certain adult populations in endemic areas, creating infection reservoirs that drive ‘bounce back’ of STH infection to pretreatment levels post-mass drug administration (MDA). Predisposition is a widespread, but poorly understood phenomena among helminth infections where individuals are predisposed to reinfection after repeated treatments.

Methods

This analysis uses Geshiyaro project data, an STH control programme exploring transmission interruption by community-wide MDA and enhanced water, sanitation and hygiene during 2019–2023. Parasitological survey data from longitudinal cohorts are analysed using Kendall's Tau-b rank correlation to assess the evidence for predisposition to light or heavy infection between four consecutive rounds of MDA.

Results

Correlation analyses revealed the strongest evidence for predisposition to heavy or light Ascaris lumbricoides infection was between survey 1 and 2 (Tau-b 0.29; p<0.001). Overall patterns were not observed for Trichuris trichiura or hookworm infections, however, some significant and notable correlations were recorded for some stratifications and time points.

Conclusions

Evidence for predisposition in endemic settings in southern Ethiopia with low STH prevalence suggests that more targeted approaches to MDA in those predisposed to infection may be a sensible control strategy if cheap, point of care diagnostics are available.
Sporodochia Formed by Fusarium oxysporum f. sp. fragariae Produce Airborne Conidia and Are Ubiquitous on Diseased Strawberry Plants in California
Authors: Henry Peter M. , Dilla-Ermita Christine J. , Goldman Polly , Jaime Jose , Ramos Gerardo
Published: March 2023

Sporodochia are dense masses of fungal hyphae bearing asexual conidia. For Fusarium oxysporum, sporodochia are known to produce airborne conidia and enhance the dissemination of this otherwise soilborne pathogen. Sporodochia are small and transient, and they are documented for only a few formae speciales of F. oxysporum. This study reports airborne conidia and sporodochia produced by F. oxysporum f. sp. fragariae, the cause of Fusarium wilt of strawberry, in the Monterey Bay region of California. Sporodochia were discovered in 21 of 24 Fusarium wilt-diseased fields surveyed for this study and were readily observed on most symptomatic plants in these fields. Only necrotic tissues bore sporodochia, and they were most frequently observed on petioles and peduncles. Sporodochia covered significantly greater lengths of peduncles than petioles, extending from the base of the plant toward the upper part of the canopy. A stolon hosted the longest stretch of sporodochial growth, found covering the stolon's entire 35-cm length and the base of the daughter plant. Macroconidia were produced by all sporodochia samples, and we did not find microconidia on any samples. An initial series of experiments confirmed the potential for conidia produced by sporodochia to disperse with wind over short distances. The prevalence of sporodochia producing airborne spores of F. oxysporum f. sp. fragariae has great importance for disease management and biosecurity.

[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Increased mitochondrial Ca2+ contributes to health decline with age and Duchene muscular dystrophy in C. elegans
Authors: Higashitani Atsushi , Teranishi Mika , Nakagawa Yui , Itoh Yukou , Sudevan Surabhi , Szewczyk Nathaniel J. , Kubota Yukihiko , Abe Takaaki , Kobayashi Takeshi
Published: March 2023

Sarcopenia is a geriatric syndrome characterized by an age‐related decline in skeletal muscle mass and strength. Here, we show that suppression of mitochondrial calcium uniporter (MCU)‐mediated Ca2+ influx into mitochondria in the body wall muscles of the nematode Caenorhabditis elegans improved the sarcopenic phenotypes, blunting movement and mitochondrial structural and functional decline with age. We found that normally aged muscle cells exhibited elevated resting mitochondrial Ca2+ levels and increased mitophagy to eliminate damaged mitochondria. Similar to aging muscle, we found that suppressing MCU function in muscular dystrophy improved movement via reducing elevated resting mitochondrial Ca2+ levels. Taken together, our results reveal that elevated resting mitochondrial Ca2+ levels contribute to muscle decline with age and muscular dystrophy. Further, modulation of MCU activity may act as a potential pharmacological target in various conditions involving muscle loss.
Psychometric Properties of the Traditional Chinese Version of the Venous Leg Ulcer Quality of Life Questionnaire
Authors: Lin Hsiao-Ching , Fang Chien-Liang , Hsu Chin-Hao , Fan Jun-Yu
Published: March 2023

OBJECTIVE

Symptoms and treatment of venous leg ulcers (VLUs) adversely impact patients’ quality of life (QoL). There is no QoL tool that considers the linguistic and cultural specificities of patients with VLU in Taiwan. This study aimed to evaluate the psychometric properties of the traditional Chinese version of the Venous Leg Ulcer Quality of Life Questionnaire (VLU-QoL).

METHODS

The processes of translation and cultural adaptation of the VLU-QoL from English to traditional Chinese included forward translation, back translation, linguistic modification, and expert review. Using a sample of 167 patients with VLU from a hospital in southern Taiwan, the psychometric properties analyzed were internal consistency, test-retest reliability, content validity, convergent validity, and criterion-related.

RESULTS

The traditional Chinese version of the VLU-QoL demonstrated good overall internal consistency (Cronbach α = .95) and overall test-retest reliability coefficient (r = 0.98). Confirmatory factor analysis was used to assess the convergent validity of the scale; results showed that the Activity, Psychology, and Symptom Distress constructs had acceptable fit and a structure similar to that of the original scale. The scale had its criterion-related validity verified using the Taiwanese version of the 36-item Short-Form Health Survey, demonstrating a good correlation coefficient r that ranged from −0.7 to −0.2 (P < .001).

CONCLUSIONS

The Chinese version of the VLU-QoL is valid and reliable for assessing the QoL in patients with VLU, delivering a tool that nurses can use to deliver timely and appropriate care to improve patients’ QoL.
Characteristics of Patients with Pressure Injuries in a COVID-19 Referral Hospital
Authors: Putri Indri Lakhsmi , Tungga Aldrich Alexander Afeli , Pramanasari Rachmaniar , Wungu Citrawati Dyah Kencono
Published: March 2023

OBJECTIVE

This retrospective study aimed to describe the characteristics of patients treated at a COVID-19 referral hospital from March 2020 to June 2021 who experienced pressure injuries (PIs) either before or after admission.

METHODS

The researchers collected and analyzed data on patients’ demographic characteristics, symptoms, comorbidities, location and severity of PI, laboratory values, oxygen therapy, length of stay, and vasopressor use.

RESULTS

During the study period, 1,070 patients were hospitalized for COVID-19 with varying degrees of severity, and 12 patients were diagnosed with PI. Eight (66.7%) of the patients with PI were men. The median age was 60 (range, 51–71) years, and half of the patients had obesity. Eleven of the patients with PI (91.4%) had at least one comorbid condition. The sacrum and gluteus were the two most commonly affected sites. Those with stage 3 PI had a substantially greater median d-dimer value (7,900 ng/mL) than patients with stage 2 PI (1,100 ng/mL). The average length of stay was 22 (range, 9.8–40.3) days.

CONCLUSIONS

Health professionals should be aware of an increase in d-dimer in patients with COVID-19 and PI. Even though PIs in these patients might not result in mortality, an increase in morbidity can be avoided with the right care.
A New Tool for Holistic Residency Application Review: Using Natural Language Processing of Applicant Experiences to Predict Interview Invitation
Authors: Mahtani Arun Umesh , Reinstein Ilan , Marin Marina , Burk-Rafel Jesse
Published: March 2023

Problem

Reviewing residency application narrative components is time intensive and has contributed to nearly half of applications not receiving holistic review. The authors developed a natural language processing (NLP)–based tool to automate review of applicants’ narrative experience entries and predict interview invitation.

Approach

Experience entries (n = 188,500) were extracted from 6,403 residency applications across 3 application cycles (2017–2019) at 1 internal medicine program, combined at the applicant level, and paired with the interview invitation decision (n = 1,224 invitations). NLP identified important words (or word pairs) with term frequency-inverse document frequency, which were used to predict interview invitation using logistic regression with L1 regularization. Terms remaining in the model were analyzed thematically. Logistic regression models were also built using structured application data and a combination of NLP and structured data. Model performance was evaluated on never-before-seen data using area under the receiver operating characteristic and precision–recall curves (AUROC, AUPRC).

Outcomes

The NLP model had an AUROC of 0.80 (vs chance decision of 0.50) and AUPRC of 0.49 (vs chance decision of 0.19), showing moderate predictive strength. Phrases indicating active leadership, research, or work in social justice and health disparities were associated with interview invitation. The model’s detection of these key selection factors demonstrated face validity. Adding structured data to the model significantly improved prediction (AUROC 0.92, AUPRC 0.73), as expected given reliance on such metrics for interview invitation.

Next Steps

This model represents a first step in using NLP-based artificial intelligence tools to promote holistic residency application review. The authors are assessing the practical utility of using this model to identify applicants screened out using traditional metrics. Generalizability must be determined through model retraining and evaluation at other programs. Work is ongoing to thwart model “gaming,” improve prediction, and remove unwanted biases introduced during model training.
Learning How to Learn: An Innovative Medical School Orientation Activity
Authors: Smith James F. , Sinclair Mary L. , Madhavan Kiely M. , Eno Cassie A. , Piemonte Nicole M.
Published: March 2023

Problem

In 2018, Creighton University School of Medicine initiated a multiyear strategy to redesign the pedagogic approach of its educational program, transitioning from large-group, lecture-based experiences to small-group, active learning experiences using case-based learning (CBL) as required prework for team-based learning (TBL). In July 2019, the authors introduced their first-year medical students to the pedagogic and empiric underpinnings of the new curriculum they would experience. Initially, and ironically, this introduction was presented as a 30-minute didactic lecture, and students’ ability to assimilate this information in any meaningful way was challenged. In addition, students required several sessions of the CBL–TBL activities during the official curriculum before they were able to effectively function as a team of learners. The authors created a novel introduction to their educational program that was active, meaningful, and efficient.

Approach

In 2022, the authors created a 2-hour, small-group CBL activity using a fictional narrative of a medical student encountering their curriculum. During development, the authors recognized that the narrative was conducive to introduction of affective responses to medical education stressors, such as imposter phenomenon and Stanford duck syndrome. The CBL activity was given 4 hours during the formal 2022 orientation; 230 students participated. The CBL activity occurred on the second day of orientation and the TBL activity on the third (final) day of orientation.

Outcomes

The results of the TBL activity indicate that students acquired a fundamental understanding of the attributes of active learning, features of imposter syndrome, substance abuse associated with Stanford duck syndrome, and peer evaluation.

Next Steps

This CBL–TBL activity will become a permanent part of orientation. The authors hope to evaluate the qualitative outcomes of this innovation on students’ professional identity formation, institutional affiliation, and motivation. The authors will assess for any negative impact of this experience and the overall orientation.
Radiological Features of Atlas Occipitalization and Its Clinical Implications
Authors: Yan Jun , Qiu Cheng , Fu Lingling , Liu Xinyu , Zheng Yanping
Published: March 2023

Study Design.

Retrospective radiographic analysis.

Objectives.

Evaluation of the anatomical features of the craniovertebral junction in patients with occipitalization with and without atlantoaxial dislocation (AAD).

Summary of Background Data.

Atlas occipitalization is a common feature of congenital AAD and usually requires surgical intervention. However, not all instances of occipitalization necessarily lead to AAD. No study has specifically examined and compared the craniovertebral bony morphology in occipitalization with, and without, AAD.

Method.

We reviewed computed tomography (CT) scans of 2500 adult outpatients. Occipitalization cases without AAD (ON) were selected. Meanwhile, a series of 20 in-patient occipitalization cases with AAD (OD) were obtained in parallel. Another 20 control cases without occipitalization were also included. Multi-directional reconstructed CT images of all cases were analyzed.

Results.

A total of 18 adults with ON were found in all 2500 outpatients (0.7%). Both anterior height (AH) and posterior height (PH) of C1 lateral mass (C1LM) in the control group were significantly larger than those in both the ON and OD groups, whereas PH in the OD group was significantly less than that in the ON group. Three morphological types of the occipitalized atlas posterior arch were identified: Type I, bilateral sides were unfused with opisthion; Type II, unilateral side was unfused with opisthion, while the other side was fused; and Type III, bilateral sides were fused with opisthion. In the ON group, 3 cases were type I (17%), 6 cases were type II (33%), and 9 cases were type III (50%). In the OD group, all 20 cases were type III (100%).

Conclusion.

Atlas occipitalization with, and without, AAD results from a distinctly different bony morphology at the craniovertebral junction. The novel classification system based on reconstructed CT images may be useful in prognosticating AAD in the setting of atlas occipitalization.
A Novel Fc-Engineered Anti-HER2 Bispecific Antibody With Enhanced Antitumor Activity
Authors: Mohammadi Mehdi , Jeddi-Tehrani Mahmood , Golsaz-Shirazi Forough , Arjmand Mohammad , Torkashvand Fatemeh , Bahadori Tannaz , Judaki Mohammad Ali , Shiravi Fariba , Ahmadi Zare Hengameh , Notash Haghighat Farzaneh , Mobini Maryam , Shokri Fazel , Amiri Mohammad Mehdi
Published: March 2023

Human epidermal growth factor receptor 2 (HER2) overexpression has been demonstrated in a variety of cancers. Targeted therapy with anti-HER2 monoclonal antibodies (mAbs) has been approved as a therapeutic modality. Despite the efficacy of mAbs in tumor treatment, many patients do not benefit from this therapeutic platform. Fragment crystallizable (Fc) engineering is a common approach to improve the efficacy of therapeutic mAbs. Five Fc-engineered mAbs have so far been approved by FDA. We have recently developed an anti-HER2 bispecific mAb, BiHT, constructed from variable domains of trastuzumab, and our novel humanized anti-HER2 mAb, hersintuzumab. BiHT displayed promising antitumor activity as potently as the combination of the parental mAbs. Here, we aimed to modify the Fc of BiHT to improve its therapeutic efficacy. The Fc-engineered BiHT (MBiHT) bound to recombinant HER2 and its subdomains with an affinity similar to BiHT. It also recognized native HER2 on different cell lines, inhibited their proliferation, downregulated HER2 expression, and suppressed downstream signaling pathways similar to BiHT. Compared with BiHT, MBiHT displayed enhanced antibody-dependent cellular cytotoxicity activity against various tumor cell lines. It also inhibited the growth of ovarian xenograft tumors in nude mice more potently than BiHT. Our findings suggest that MBiHT could be a potent therapeutic candidate for the treatment of HER2-overexpressing cancer types.
Random Skin Biopsy for Diagnosis of Intravascular Large B-Cell Lymphoma: A Case Report and Literature Review
Authors: Lv Yuanjie , Xu Lingen , Liu Xiaoping , Wang Yaling
Published: March 2023

Background:

Intravascular large B-cell lymphoma (IVLBCL) is a rare, aggressive B-cell lymphoma. The heterogeneity of its clinical symptoms makes it hard to be diagnosed. The diagnosis is followed by pathological examination of affected tissues and organs including skin, central nervous system, and bone marrow. Random skin biopsy (RSB) with high sensitivity and less invasiveness becomes a common method for diagnosis in suspected patients without skin lesions.

Case report:

We reported the case of a 67-year-old man who complained of fever, dizziness, unsteady gait, numbness in both lower extremities, and incontinence. Blood routine examination suggested elevated levels of lactate dehydrogenase. Enhanced magnetic resonance imaging of the head and thoracolumbosacral spine, next-generation sequencing in blood, cerebrospinal fluid collection, bone marrow aspiration, and positron emission tomography–computed tomography presented no evidence of solid tumors. However, there were intravascular tumor cell growth and morphosis as determined by RSB. CD20, CD79a, CD5, BCL-6, and BCL-2 were positive as tested by immunohistochemistry, and Ki-67 showed high proliferative activity. Taking the medical history as an element, the patient received a diagnosis of IVLBCL. After he completed 3 cycles of RCDOP + orelabrutinib, his general condition improved.

Conclusion:

IVLBCL is an aggressive, lethal cancer that is difficult to diagnose; therefore, it is recommended for the suspected patients to receive RSB promptly and early treatment at the earliest opportunity to achieve amelioration in prognosis.
A Rare Case of Hydrophilic Polymer Embolization After Transcatheter Aortic Valve Replacement
Authors: Shefler Alanna , Blaszak Scott C. , Shea Christopher R. , Chadha Angad A.
Published: March 2023

Endovascular procedures that use a hydrophilic polymer-coated device carry a risk of embolization and ischemic complications when used intravascularly. Because these coatings are increasingly used worldwide, it is important to identify potential adverse effects early. Cutaneous complications of hydrophilic polymer emboli are rare and not commonly described in the literature. Therefore, we report a case of hydrophilic polymer embolization with cutaneous findings in a patient who underwent a recent transcatheter aortic valve replacement.
Lack of sex and estrous stage effects on compulsive behavior assessed using a schedule-induced polydipsia procedure in rats
Authors: Park-Oates Min , Prus Adam J.
Published: March 2023

Preclinical behavior models used for screening pharmacological treatments for mental disorders have generally used only male research subjects, and for studies that have included female subjects, few have utilized sex as a study variable. In fact, many mental disorders vary by prevalence and symptomatology between sexes, creating a need to evaluate established subject models for sex differences. Compulsive behavior is a feature shared across many mental disorders and effective treatments have been examined pre-clinically using the schedule-induced polydipsia procedure in rats. Drugs effective for reducing polydipsia include psychostimulants, such as d-amphetamine. Virtually no studies have examined sex differences using this procedure. For the present study, male and female rats were examined in the schedule-induced polydipsia paradigm. Rats were food-restricted and trained on a fixed-interval food reinforcement schedule and given free access to water during experimental sessions. Estrous stages were assessed during training and test sessions. The psychostimulant d-amphetamine was also tested once stable water consumption occurred. Excessive water intake developed over the course of training. Females required significantly more sessions to reach a stable level of drinking. Treatment with d-amphetamine (1.0 mg/kg, but not 0.25 or 0.5 mg/kg) significantly reduced drinking in both male and female rats. No sex differences were observed across other study variables including comparisons between diestrus and proestrus stages. Overall, these findings suggest that schedule-induced polydipsia procedures that employ similar methods can produce results generalizable across male and female subjects.
Histamine and its H1 receptors in the ventral pallidum mediate formalin-induced pain-related behaviors through this region and spinal cord opioid receptors
Authors: Asgharieh-Ahari Morteza , Tamaddonfard Esmaeal , Erfanparast Amir , Soltanalinejad-Taghiabad Farhad
Published: March 2023

Many structures of the central nervous system recruit different neurotransmitters in pain processing. This study focused on the contribution of histamine and its H1 receptors in the ventral pallidum (VP) in mediating pain-triggered behaviors. Intra-VP microinjection of histamine and 2-pyridylethylamine (2-PEA, a histamine H1 receptor agonist) at the same doses of 0.5 and 1 µg/200 nl reduced both the first and second phases of licking/biting duration as well as flinching number induced by intra-plantar (ipl) injection of formalin (2.5%, 50 µl). Premicroinjection of mepyramine (a histamine H1 antagonist, 2 µg/200 nl) into the VP antagonized the suppressive effects of 1 µg/200 nl histamine and 2-PEA on licking/biting and flinching behaviors. The possible mechanisms of the above-mentioned pain-reducing effects were followed by intra-VP and intrathecal administration of naloxone (an opioid receptor antagonist). Naloxone (2 µg/200 nl) preadministration into the VP inhibited attenuating effects of histamine and 2-PEA on both the licking/biting and flinching behaviors, whereas intrathecal injection of naloxone only inhibited their suppressing effects on flinching behavior. None of the treatments used in this study altered the animal’s motor activity. The obtained results may reveal the role of histamine and its activated H1 receptor in the VP in suppressing the pain behaviors caused by formalin. Opioid receptors in the VP and spinal cord may contribute to these functions.
Participant Perspectives on Community Health Workers' Critical Role in Their Experience of the Pathways Program to Address Complex Needs
Authors: Roth Sarah E. , Marsi Katherine , Gronowski Ben , Cohen-Cline Hannah , Kenton Natalie
Published: March 2023

This study aimed to describe participants' experiences of Pathways, a community hub care coordination model, including its impact on their lives and their relationship with the Pathways community health worker (CHW). The research team conducted semistructured, in-depth interviews with Pathways participants (n = 13) and analyzed interviews using thematic analysis. Interviews reveal how Pathways helps individuals navigate systems more confidently, increases access to needed resources, and improves well-being. CHWs defined participants' experience, providing a safe, reliable setting to make progress toward goals. Our findings support the evidence base for Pathways as an effective model of care coordination for people with complex needs.
Lessons Learned From Frontline Nurses
Authors: Manney Devon J. , Sands Kristy A. , Fazzino David
Published: March 2023

The COVID-19 pandemic has compounded the stress level of nurses and the nursing shortage. In addition, the disruption of bedside clinical experiences has raised concerns about the preparedness of nurses entering practice. A mixed methods study was conducted to learn about the perceptions of frontline nurses during the COVID-19 pandemic. Findings revealed implications for nurses in professional development as they are challenged to reimagine new nurse orientation and meet the needs of graduates transitioning to practice.
LYMPH NODE TRANSFER AND NEO-LYMPHANGIOGENESIS. FROM THEORY TO EVIDENCE
Authors: Maruccia Michele , Giudice Giuseppe , Ciudad Pedro , Manrique Oscar J , Cazzato Gerardo , Chen Hung-Chi , Elia Rossella
Published: March 2023

BACKGROUND.

Vascularized lymph node transfer (VLNT) has proven to be a valuable treatment for patients affected by advanced stages of lymphedema. Although a spontaneous neo-lymphangiogenesis has been advocated to explain the positive effects of VLNT, there is still a lack of supportive biological evidence. The aim of the paper was to demonstrate the post-operative formation of new lymphatic vessels using histological skin sections from the lymphedematous limb.

MATERIALS AND METHODS.

All patients diagnosed with extremities’ lymphedema who had undergone gastroepiploic vascularized lymph node flap (GE-VLN) between January 2016 and December 2018 were identified. Full thickness 6-mm skin punch biopsies were obtained from all voluntary patients at identical sites of the lymphedematous limb (during the surgical procedure of VLNT (T0) and 1 year later (T1). The histological samples were prepared to be immunostained with Anti-Podoplanin / gp36 antibody.

RESULTS.

The study analyzed the results of 14 lymph node transfer voluntary patients. At 12 months of follow-up, the mean circumference reduction rate was 44.3 ± 4.4 at above elbow/above knee level (AE/AK) and 60.9 ± 7 at below elbow/below knee level (BE/BK) Podoplanin expression values were on average 7.92 ± 1.77 (vessels/mm2) at time 0 and 11.79 ± 3.38 (vessels/mm2) at T1. The difference was statistically significant between pre-operative and post-operative values (p=0.0008)

CONCLUSION.

The present study provides anatomic evidence that a neo-lymphangiogenetic process is induced by the VLNT procedure as new functional lymphatic vessels can be detected in close proximity to the transferred lymph nodes.
Fronto-facial surgery: reducing infection with the development and 6-year outcome of a fronto-facial protocol.
Authors: White Andrea , van de Lande Lara S. , O’Hara Justine , Hartley John , Hayward Richard , James Greg , Jeelani N. Owase , Dunaway David J.
Published: March 2023

Background:

Frontofacial surgery (FFS) creates a communication between the cranial and nasal cavities and is associated with significant infection risk. After a cluster of infections affecting patients undergoing FFS a root cause analysis of index cases was undertaken but no specifically remedial causes identified. Basic principles incorporating known risk factors for the prevention of surgical site infection were then applied to the creation of a peri-operative management protocol. This study analyses infection rates before and after its implementation.

Methodology:

The protocol was designed around the needs of patients undergoing FFS and consists of three checklists covering their pre-, intra- and post-operative care. Compliance required the completion of each checklist. All patients undergoing FFS between 1999 to 2019 were studied retrospectively and infections occurring before and after the implementation of the protocol analysed.

Results:

103 patients underwent FFS (60 monobloc and 36 facial bipartition) prior to the implementation of the protocol in August of 2013, and 30 patients after its implementation. Compliance with the protocol was 95%. Following implementation there was a statistically significant reduction in infections from 41.7% to 13.3% (p=0.005).

Conclusion:

Although no specific aetiology for a cluster of post-operative infection had been identified, the implementation of a bespoke protocol consisting of pre-, peri- and post-operative checklists covering measures known to reduce infection risk was associated with a significant reduction in post-operative infections in patients undergoing FFS.
Comparison of Facial Growth Between Two Nasoalveolar Molding Techniques in Unilateral Complete Cleft Lip Patients: A Randomized, Prospective, Single-blind Trial
Authors: Chang Frank Chun-Shin , Huang Jung-Ju , Wallace Christopher Glenn , Hsiao Yen-Chang , Chen Zung-Chung , Liao Yu-Fang , Chen Philip Kuo-Ting
Published: March 2023

Background:

Nasoalveolar molding (NAM) has become standard treatment in our Craniofacial Center. Two types of pre-surgical NAM, Grayson technique and Figueroa technique, co-exist. We previously found no differences in number of clinic visits, cost and 6 months post-operative outcome between the two techniques. Since Figueroa’s method involves passive, whilst Grayson’s method involves active, alveolar molding, we extended the previous study to evaluate facial growth between these two groups.

Methods:

This randomized, prospective, single-blind study, conducted between May 2010 and March 2013, recruited 30 patients with unilateral complete cleft lip and palate patients and randomized them for Grayson or Figueroa pre-surgical NAM. Their standard lateral cephalometric measurements at 5 years were used to determine facial growth.

Results:

Twenty-nine patients completed 5 years of follow-up. There were no statistical differences in facial cephalometric measurements between the two groups.

Conclusion:

Pre-surgical NAM using either passive or active NAM technique produced similar facial growth patterns after unilateral cleft lip and palate repair.
A phase 3 study of safety and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine, followed by 23-valent pneumococcal polysaccharide vaccine, in children with HIV
Authors: Wilck Marissa , Barnabas Shaun , Chokephaibulkit Kulkanya , Violari Avy , Kosalaraksa Pope , Yesypenko Svitlana , Chukhalova Iryna , Dagan Ron , Richmond Peter , Mikviman Elena , Morgan Leslie , Feemster Kristen , Lupinacci Robert , Chiarappa Joseph , Madhi Shabir A. , Bickham Kara , Musey Luwy
Published: March 2023

Objectives:

To evaluate the safety and immunogenicity of V114 [15-valent pneumococcal conjugate vaccine (PCV) containing serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9 V, 14, 18C, 19A, 19F, 22F, 23F, 33F], followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23) 8 weeks later, in children with HIV.

Design:

This phase 3 study (NCT03921424) randomized participants 6–17 years of age with HIV (CD4+ T-cell count ≥200 cells/μl, plasma HIV RNA <50 000 copies/ml) to receive V114 or 13-valent PCV (PCV13) in a double-blind manner on Day 1, followed by PPSV23 at Week 8.

Methods:

Adverse events (AEs), pneumococcal serotype-specific immunoglobulin G (IgG), and opsonophagocytic activity (OPA) were evaluated 30 days after each vaccination.

Results:

The proportion of participants experiencing at least one AE post-PCV was 78.8% in the V114 group (n = 203) and 69.6% in the PCV13 group (n = 204); respective proportions post-PPSV23 were 75.4% (n = 203) and 77.2% (n = 202). There were no vaccine-related serious AEs. IgG geometric mean concentrations (GMCs) and OPA geometric mean titers (GMTs) were generally comparable between V114 and PCV13 for shared serotypes at Day 30, and were higher for V114 compared with PCV13 for the additional V114 serotypes 22F and 33F. Approximately 30 days after PPSV23, IgG GMCs and OPA GMTs were generally comparable between the V114 and PCV13 groups for all 15 serotypes in V114.

Conclusions:

In children with HIV, a sequential administration of V114 followed 8 weeks later with PPSV23 is well tolerated and induces immune responses for all 15 pneumococcal serotypes included in V114.
Effectiveness of Cross-Linked Acellular Dermal Matrix to Correct Post-Traumatic Enophthalmos
Authors: Park Tae Hwan
Published: March 2023

Background:

The use of an acellular dermal matrix is rarely reported in orbital wall fracture reconstruction. This study aimed to share the author’s experience with the cross-linked acellular dermal matrix as an allograft material for enophthalmos correction.

Methods:

In this retrospective study, the author evaluated the medical records and 3-dimensional facial computed tomography scans of patients with enophthalmos caused by neglected orbital fractures between May 2021 and June 2022. Facial computed tomography scans confirmed the clinical diagnosis of enophthalmos. A single surgeon performed all surgical operations. In all patients, the author accessed the orbital floor via subciliary incision while approaching the medial wall with a retrocaruncular incision. After fully exposing the lesion, the author used a 1.0-mm-thick cross-linked acellular dermal matrix (ADM) (MegaDerm; L&C Bio, South Korea). After trimming the cross-linked ADM to a proper size, the author implanted the ADM into the lesion.

Results:

During May 2021 and June 2022, 3 cases of enophthalmos were successfully corrected with cross-linked ADM at the author’s hospital. All patients were improved clinically and radiologically.

Conclusion:

This is the first study to show the effectiveness of cross-linked ADM for the correction of enophthalmos.
Current considerations for fetal alcohol spectrum disorders: identification to intervention
Authors: Glass Leila , Moore Eileen M. , Mattson Sarah N.
Published: March 2023

Purpose of review

This review highlights recent findings regarding the prevalence, public health impact, clinical presentation, intervention access and conceptualization of fetal alcohol spectrum disorders (FASDs). Despite ongoing work in prevention and identification of this population, the rates of drinking during pregnancy have increased and significant gaps remain in diagnosis and intervention.

Recent findings

Prenatal alcohol exposure is the most common preventable cause of developmental disability in the world. Research has focused on improving diagnostic clarity, utilizing technology and neuroimaging to facilitate identification, engaging broader stakeholders (including self-advocates) to inform understanding and needs, and increasing access to effective interventions. There is an emerging focus on developmental trajectories and experiences in young and middle adulthood. Public policy advocacy has also made great strides in recent years.

Increases in public awareness, greater concordance of diagnostic schema, leveraged use of novel technology, and the development of targeted interventions within a holistic, strengths-based conceptualization are important considerations for this population.
Gaps in modelling animal migration with evolutionary game theory: infection can favour the loss of migration
Authors: Shaw Allison K. , Torstenson Martha , Craft Meggan E. , Binning Sandra A.
Published: March 2023

Ongoing environmental changes alter how natural selection shapes animal migration. Understanding how these changes play out theoretically can be done using evolutionary game theoretic (EGT) approaches, such as looking for evolutionarily stable strategies. Here, we first describe historical patterns of how EGT models have explored different drivers of migration. We find that there are substantial gaps in both the taxa (mammals, amphibians, reptiles, insects) and mechanisms (mutualism, interspecific competition) included in past EGT models of migration. Although enemy interactions, including parasites, are increasingly considered in models of animal migration, they remain the least studied of factors for migration considered to date. Furthermore, few papers look at changes in migration in response to perturbations (e.g. climate change, new species interactions). To address this gap, we present a new EGT model to understand how infection with a novel parasite changes host migration. We find three possible outcomes when migrants encounter novel parasites: maintenance of migration (despite the added infection cost), loss of migration (evolutionary shift to residency) or population collapse, depending on the risk and cost of getting infected, and the cost currency. Our work demonstrates how emerging infection can alter animal behaviour such as migration.

This article is part of the theme issue ‘Half a century of evolutionary games: a synthesis of theory, application and future directions’.
Accurate prediction of transcriptional activity of single missense variants in HIV Tat with deep learning
Authors: Derbel Houssemeddine , Giacoletto CJ , Benjamin Ronald , Chen Gordon , Schiller Martin R. , Liu Qian
Published: March 2023

Tat is an essential gene for increasing the transcription of all HIV genes, and it affects HIV replication, HIV exit from latency, and AIDS progression. The Tat gene frequently mutatesin vivoproducing variants with diverse activities, contributing to HIV viral heterogeneity, as well as drug-resistant clones. Thus, identifying the transcriptional activities of Tat variants will help to better understand AIDS pathology and treatment. We recently reported the missense mutation landscape of all single amino acid Tat variants. In these experiments, a fraction of double missense alleles exhibited intragenic epistasis. It is too time-consuming and costly to determine a variants’ effect for all double mutant alleles with experiments. Therefore, we propose a combined GigaAssay/Deep learning approach. As a first step for determining activity landscapes for complex variants, we evaluated a deep learning framework using previously reported GigaAssay experiments to predict how transcription activity is affected by Tat variants with single missense substitutions. Our approach achieves a 0.94 Pearson correlation coefficient when comparing experimental to predicted activities. This hybrid approach should be extensible to more complex Tat alleles for better understanding the genetic control of HIV genome transcription.
Single-cell transcriptomics identifies different immune signatures between macrophage activation-like syndrome and immune paralysis in sepsis
Authors: Grondman Inge , Koeken Valerie A.C.M. , Karageorgos Athanasios , Li Wenchao , Antonakos Nikolaos , Zhang Bowen , Damoraki Georgia , Xu Cheng-Jian , Giamarellos-Bourboulis Evangelos J. , Li Yang , Netea Mihai G.
Published: March 2023

Different immune phenotypes characterize sepsis patients, including hyperinflammation and/or immunosuppression, but the biological mechanisms driving this heterogeneity remain largely unknown. We used single-cell RNA sequencing to profile circulating leukocytes of healthy controls and sepsis patients classified as eitherhyperinflammatory(macrophage activation-like syndrome [MALS]),immune paralysis, orunclassified(when criteria for neither of these two immune subgroups were applicable). Pronounced differences were detected in the transcriptional signature of monocytes from sepsis patients, with clear distinction between MALS and immune paralysis patients. Unsupervised clustering analysis revealed the existence of MALS-specific monocyte clusters, as well as one sepsis-specific monocyte cluster that was linked to disease severity. In separate cohorts, urosepsis was characterized by heterogeneous MALS and immunosuppression monocyte signatures, while MALS-specific monocyte clusters showed overlapping transcriptional signatures with severe COVID-19. In conclusion, our findings shed light on the heterogeneous immune landscape underlying sepsis, and provide opportunities for patient stratification for future therapeutic development.
A Tyrosine Phospho-switch within the Longin Domain of VAMP721 modulates SNARE functionality
Authors: Ricardi Martiniano Maria , Wallmeroth Niklas , Cermesoni Cecilia , Mehlhorn Dietmar Gerald , Richter Sandra , Zhang Lei , Mittendorf Josephine , Godehardt Ingeborg , Berendzen Kenneth Wayne , von Roepenack-Lahaye Edda , Stierhof York-Dieter , Lipka Volker , Jürgens Gerd , Grefen Christopher
Published: March 2023

The final step in secretion is membrane fusion facilitated by SNARE proteins that reside in opposite membranes. The formation of a trans-SNARE complex between one R and three Q coiled-coiled SNARE domains drives the final approach of the membranes providing the mechanical energy for fusion. Biological control of this mechanism is exerted by additional domains within some SNAREs. For example, the N-terminal Longin domain (LD) of R-SNAREs (also called Vesicle-associated membrane proteins, VAMPs) can fold back onto the SNARE domain blocking interaction with other cognate SNAREs. The LD may also determine the subcellular localization via interaction with other trafficking related proteins. Here, we provide cell-biological and genetic evidence that phosphorylation of the Tyrosine57 residue regulates the functionality of VAMP721. We found that an aspartate mutation mimics phosphorylation, leading to protein instability and subsequent degradation in lytic vacuoles. The mutant SNARE also fails to rescue the defects ofvamp721vamp722loss-of-function lines in spite of its wildtype-like localization within the secretory pathway and the ability to interact with cognate SNARE partners. Most importantly, it imposes a dominant negative phenotype interfering with root growth, normal secretion and cytokinesis in wildtype plants generating large aggregates that mainly contain secretory vesicles. Non-phosphorylatable VAMP721Y57Fneeds higher gene dosage to rescue double mutants in comparison to native VAMP721 underpinning that phosphorylation modulates SNARE function. We propose a model where a short-lived phosphorylation of Y57 serves as a regulatory step to control VAMP721 activity, favouring its open state and interaction with cognate partners to ultimately drive membrane fusion.