bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcomes of Open Bleb Revision After PreserFlo MicroShunt Failure in Patients With Glaucoma
Authors: Strzalkowska Alicja , Strzalkowski Piotr , Hoffmann Esther M. , Pfeiffer Norbert , Schuster Alexander K.
Published: June 2023

Précis:

After the open bleb revision following PreserFlo, the mean postoperative intraocular pressure (IOP) was lowered from 26.4 ± 9.9 mm Hg to 12.9 ± 5.6 mm Hg at 1 month and 15.9 ± 4.1 mm Hg at 12 months.

Purpose:

The purpose of this study was to evaluate the effectiveness and safety of an open bleb revision with mitomycin-C(MMC) for bleb fibrosis after PreserFlo MicroShunt implantation.

Patients and Methods:

We performed a retrospective analysis of 27 consecutive patients with bleb fibrosis after PreserFlo MicroShunt Implantation that underwent an open revision with MMC 0.2 mg/mL applied for 3 minutes at the Department of Ophthalmology of the Mainz, University Medical Center, Mainz, Germany. Demographic data, such as age, sex, glaucoma type, number of glaucoma medications, IOP before and after PreserFlo implantation and revision, complications, and reoperations within 12 months, were analyzed.

Results:

Twenty-seven patients (27 eyes) received an open revision after previous PreserFlo Microshunt implantation and consecutive bleb fibrosis. The mean preoperative IOP was 26.4 ± 9.9 mm Hg before revision, 7.0 ± 2.7 mm Hg (P< 0.001) in the first week after the revision, and 15.9 ± 4.1 mm Hg at 12 months (P= 0.02). Four patients needed IOP-lowering medication after 12 months. One patient had a positive Seidel test and needed a conjunctival suture. Four patients required a second procedure due to recurring bleb fibrosis.

Conclusions:

At 12 months, open revision with MMC for bleb fibrosis after failed PreserFlo implantation effectively and safely reduced IOP with a similar medication burden.
Thrombospondin Mutations and Patients With Primary Congenital Glaucoma in a United States Population
Authors: Boese Erin A. , Alward Wallace L.M. , Kwon Young H. , Roos Ben R. , Stone Edwin M. , Scheetz Todd. E. , Fingert John H.
Published: June 2023

Mutations in the thrombospondin 1 (THBS1) gene have been previously reported in primary congenital glaucoma (PCG) pedigrees that exhibit autosomal dominant inheritance with low penetrance. We sought to determine the role of THBS1 mutations in a cohort of 20 patients with PCG and 362 normal controls from Iowa using a combination of Sanger sequencing and whole exome sequencing. We detected 16 different THBS1 variants, including 4 rare, nonsynonymous variants (p.Thr611Met, p.Asn708Lys, p.Gln1089His, and p.Glu1166Lys). However, none of these variants were judged to be disease-causing mutations based on: 1) prevalence in cases and controls from Iowa, 2) prevalence in the public database gnomAD, 3) mutation analysis algorithms, and 4) THBS1 DNA sequence conservation. These results indicate THBS1 mutations are not a common cause of PCG in patients from Iowa and may be a rare cause of PCG overall.
Mismatched opioid prescription in patients discharged after neurological surgeries: a retrospective cohort study
Authors: Campbell Liam J. , Mummaneni Praveen V. , Letchuman Vijay , Langnas Erica , Agarwal Nitin , Guan Lucy S. , Croci Rhiannon , Vargas Enrique , Reisner Lori , Bickler Phil , Chou Dean , Chang Edward , Guan Zhonghui
Published: June 2023

Although postsurgical overprescription has been well-studied, postsurgical opioid underprescription remains largely overlooked. This retrospective cohort study was to investigate the extent of discharge opioid overprescription and underprescription in patients after neurological surgeries. Six thousand nine hundred forty-nine adult opioid-naive patients who underwent inpatient neurosurgical procedures at the University of California San Francisco were included. The primary outcome was the discrepancy between individual patient's prescribed daily oral morphine milligram equivalent (MME) at discharge and patient's own inpatient daily MME consumed within 24 hours of discharge. Analyses include Wilcoxon, Mann–Whitney, Kruskal–Wallis, and χ2 tests, and linear or multivariable logistic regression. 64.3% and 19.5% of patients were opioid overprescribed and underprescribed, respectively, with median prescribed daily MME 360% and 55.2% of median inpatient daily MME in opioid overprescribed and underprescribed patients, respectively. 54.6% of patients with no inpatient opioid the day before discharge were opioid overprescribed. Opioid underprescription dose-dependently increased the rate of opioid refill 1 to 30 days after discharge. From 2016 to 2019, the percentage of patients with opioid overprescription decreased by 24.8%, but the percentage of patients with opioid underprescription increased by 51.2%. Thus, the mismatched discharge opioid prescription in patients after neurological surgeries presented as both opioid overprescription and underprescription, with a dose-dependent increased rate of opioid refill 1 to 30 days after discharge in opioid underprescription. Although we are fighting against opioid overprescription to postsurgical patients, we should not ignore postsurgical opioid underprescription.
Pulmonary aspergillus infection with abnormal imaging successfully treated with omalizumab: A case report
Authors: He Xing , Chang Zhenzhen , Yan Haiying , Weng Yang
Published: June 2023

Background:

Pulmonary aspergillosis is a pulmonary infectious disease that is clinically difficult to diagnose and treat. When the lower respiratory tract is invaded by Aspergillus, the clinical manifestations and imaging features vary among patients with different immune states. The use of antifungal drugs and glucocorticoids are important, but some patients do not respond satisfactorily to treatment.

Case presentation:

A 59-year-old female had a long history of asthma and poor symptom control, with long-term use of long-acting inhaled glucocorticoids combined with a long-acting β2 receptor agonists (ICS + LABA) (salmeterol fluticasone inhalation powder). The ground glass shadow, tree-in-bud sign, and bronchiectasis in the middle lobe of the right lung and the lower lobe of both lungs were first detected by chest CT over 5 years ago. Atelectasis in the middle lobe of the right lung was detected over 3 years ago. Over 2 years ago, the patient was hospitalized and a repeat chest CT showed persistent atelectasis in the middle lobe of the right lung, and more lesions in bilateral lower lungs than before. Aspergillus fumigatus was detected in alveolar lavage fluid and sputum pathogenic culture, which confirmed the diagnosis of pulmonary aspergillosis. After treatment with voriconazole and amphotericin B, the middle lobe of the right lung partially reopened, but the lesions in bilateral lower lungs persisted. After 21 weeks of treatment, the antifungal drugs were stopped because the patient refused to use oral/intravenous glucocorticoids, and omalizumab was finally chosen for treatment. After 1 month of treatment, the patient’s clinical symptoms began to ease. After 1 year of treatment, imaging reexamination of lung showed that the lesions were completely cleared, accompanied by significant improvement in nutritional status and airway function.

Conclusions:

We reported the case of a patient with pulmonary Aspergillus infection who was treated with omalizumab and showed significant improvement in clinical symptoms and imaging abnormalities, which provides a new option for patients with pulmonary Aspergillus infection who show unsatisfactory response with first-line drugs.
Hypercalcemia during initiation of antiretroviral therapy in human immunodeficiency virus and Leishmania coinfection: A case report
Authors: Yu Tammy , Tang Jie
Published: June 2023

Rationale:

Hypercalcemia is a common complication of many granulomatous diseases but is not typically associated with leishmaniasis. Here we report an unusual case of hypercalcemia during the initiation of antiviral therapy in a patient with acquired immunodeficiency syndrome coinfected with visceral leishmaniasis.

Patient Concerns:

Our patient presented with malaise and altered mental status following antiretroviral therapy initiation. He was found to have de novo hypercalcemia complicated by acute kidney injury.

Diagnosis, interventions, and outcomes:

An extensive workup for other etiologies of hypercalcemia was negative. The patient was ultimately thought to have hypercalcemia secondary to visceral leishmaniasis in the setting of immune reconstitution inflammatory syndrome. He was treated with intravenous volume expansion, bisphosphonates, and oral corticosteroid therapy with complete resolution.

Lessons:

This case highlights an unusual presentation of immune reconstitution inflammatory syndrome, in which proinflammatory cytokine signaling during the restoration of cellular immunity may have led to increased ectopic calcitriol production by granuloma macrophages, thereby altering bone-mineral metabolism and driving hypercalcemia.
Clinical trial of manual therapy in the treatment of chondromalacia patellae
Authors: Cai Yan , Deng Ying , Ou Liang , Guo Yuxing , Guo Yanxing
Published: June 2023

Background:

Chondromalacia patellae (CP) is a common and main cause of knee pain, the prevalence of the disease in the general population is as high as 36.2%, especially in middle-aged patients aged between 30 and 40 years (up to 50%). The use of manual therapy (MT) to dredge the meridians and muscles around the knee joint and stimulate the relevant acupoints can play vital roles in relieving pain and improving function. The purpose of this study is to assess the effectiveness, safety and further comprehensively, completely and multi-dimensionally explain the mechanism and treatment advantages of MT for CP.

Methods:

A prospective randomized controlled clinical trial design was used to study the efficacy and safety of MT in the treatment of CP. One hundred and twenty cases of CP patients will be recruited and randomly divided into experimental group and control group according to 1:1. The control group: sodium hyaluronate; experimental group: MT added on the basis of the control group. Both groups will receive standard treatment for 4 weeks and followed up for 3 months. And at the same time, pay attention to its efficacy and safety indicators. Observation indicators include: the visual analogue scale pain score; the Western Ontario and McMaster Universities Arthritis Index scores; the Lysholm scores, and Bristol scores, adverse reactions, etc. Data analysis was performed using SPSS 25.0 software.

Discussion:

This study will precisely evaluate the effectiveness and safety of MT in the treatment of CP. The results of this experiment will provide more reliable clinical basis for the selection of MT for patients with CP.
Use of extracorporeal membrane oxygenation in children with burn injury: Case report and literature review
Authors: Wang Yanfei , Deng Kelei , Qian Junjie , Tan Linhua
Published: June 2023

Rationale:

Burns are one of the most debilitating injuries in the world and one of the major causes of accidental disability and death among children. Severe burns can result in irreversible brain damage, placing patients at high risk of brain failure and high mortality. Therefore, timely diagnosis and treatment of burn encephalopathy are crucial for improving prognosis. In recent years, extracorporeal membrane oxygenation (ECMO) has been increasingly used to improve the prognosis of patients with burns. Here, we report a case of ECMO treatment in a child with burns and review the relevant literature.

Patient concerns:

A 7-year-old boy with a modified Baux score of 24 presented with asphyxia, loss of consciousness, refractory hypoxemia, and malignant arrhythmia after smoke inhalation for 1 day. Fiberoptic bronchoscopy revealed a large amount of black carbon-like substances aspirated from the trachea.

Diagnoses:

Considering that the boy inhaled a large amount of smoke, the clinical manifestation was unclear consciousness, laboratory examination revealed continuous low blood oxygen saturation, and bronchoscopy revealed a large amount of black carbon-like substances in the trachea, thereby leading to the diagnosis of asphyxia, inhalation pneumonia, burn encephalopathy, multiple organ dysfunction syndrome, and malignant arrhythmia. In addition, pulmonary edema and carbon monoxide poisoning are caused by chemical agents, gas fumes, and vapors.

Interventions:

The boy’s blood oxygen saturation and blood circulation remained unstable despite various ventilation methods and medications, thus we decided to use ECMO. After 8 days of ECMO support, the patient was successfully weaned from the machine.

Outcomes:

Under the application of ECMO, the respiratory and circulatory systems significantly improved. Nevertheless, due to the progressive brain injury caused by burns and the poor prognosis, the parents ceased all treatment and the boy passed away.

Lessons:

This case report demonstrates that brain edema and herniation can arise as phenotypes of burn encephalopathy, which is a challenge to treat in children. Children with confirmed or suspected burn encephalopathy should undergo diagnostic tests completed as soon as possible to confirm the diagnosis. After receiving ECMO treatment, the respiratory and circulatory systems of the burn victims reported significantly improved. Hence, ECMO is a viable alternative for supporting patients with burns.
Recurrent trichilemmal carcinoma of the periorbital region treated with IMRT radiotherapy: A case report and a review of literature
Authors: Gao Shan , Xu Qin , Lan Yanli , He Lang
Published: June 2023

Rationale:

Trichilemmal carcinoma (TLC) is a rare malignant cutaneous adnexal tumor usually accept surgery. This report describes an elderly patient with recurrence TLC of the periorbital region after surgery who was subsequently treated with IMRT radiotherapy. After 2-years follow-up visit, there was no progress or metastasis.

Introduction:

TLC is a rare malignant cutaneous adnexal tumor. It usually occurs on sun-exposed areas in elderly people but rarely occurs in the periorbital region. Most cases accept surgery or micrographic Mohs surgery. Recurrence or metastasis of this neoplasm was seldom reported in the medical literature after enough tumor-free margin surgery. And radiotherapy was seldom reported in the treatment for patients of TLC.

Patient concerns:

Here we report an elderly patient with recurrence TLC of the periorbital region after surgery who was subsequently treated with radiotherapy with a total dose of 66 Gy. Two years later, the patient was admitted head, neck, chest, abdomen CT scan, and no progress or metastasis was detected after 2-years follow-up.

Diagnosis:

Trichilemmal carcinoma of the periorbital region.

Interventions:

We describe the clinical characteristics, pathological features, and choice of examination methods of a patient with TLC in the periorbital region. And we use the radical radiotherapy to treat this case.

Outcomes:

There are no progress or metastasis after 2-years follow-up.

Conclusion:

Radiotherapy is a good option for patients with TLC if the patient refuses surgery or fails to achieve a satisfactory tumor-free margin or relapses after surgery.
Interface of Clinical Nurse Specialist Practice and Healthcare Technology
Authors: Smith Justin M. , Pearson Kristina K. , Roberson Amy E.
Published: June 2023

Purpose

This article demonstrates the leadership role of the clinical nurse specialist in developing and implementing healthcare technology across the continuum of care.

Description

Three virtual nursing practices—facilitated self-care, remote patient monitoring, and virtual acute care nursing—illustrate how the clinical nurse specialist is well suited to transform traditional practice models to ones that use healthcare technology effectively. These 3 practices use interactive healthcare technology to gather patient data and allow communication and coordination with the healthcare team to meet patient-specific needs.

Outcome

Use of healthcare technology in virtual nursing practices led to early care team intervention, optimized care team processes, proactive patient outreach, timely access to care, and reduction in healthcare-associated errors and near-miss events.

Conclusion

Clinical nurse specialists are well positioned to develop innovative, effective, accessible, and high-quality virtual nursing practices. Integrating healthcare technology with nursing practice augments care for various patients, ranging from those with low illness severity in the outpatient setting to acutely ill patients in the inpatient hospital environment.
Resolution of Anastomotic Ulceration and Profound Bleeding by Endoscopic Cauterization and Oral Budesonide
Authors: Xi Dong , Hakar Melanie , Davis Jessica , Lin Henry
Published: June 2023

Anastomotic ulceration is a known complication of short gut syndrome, which can be complicated by concurrent iron deficiency and chronic bleeding. Diagnosis is confirmed through endoscopy, typically performed for the investigation of severe anemia. Inflammatory colitis in short gut syndrome has been previously reported; therefore, it is important to treat both ulceration and inflammation. Currently, no effective therapies are available. Herein, we describe the case of a child with short gut syndrome who subsequently developed anastomotic ulcers with recurrent severe bleeding and was successfully treated with endoscopic argon plasma cauterization for circumferential ulcerations, followed by a prolonged course of oral enteric budesonide. This intervention could be a potential and beneficial nonsurgical treatment for anastomotic ulceration.
Patient’s Perceptions of Importance of Discontinuing Antithrombotic Medication Before Oculoplastics Surgery
Authors: Pederson Addie , Iweh Marvelyn , Santineau Kaitlyn , Cole Travis , Freedman Kenn , Ray Coby
Published: June 2023

This study aims to analyze patients’ perspectives to ultimately gain insight into the patients understanding in 3 broad categories: their understanding of how their medications, supplements, and over-the-counter drugs work, their understanding of the risks these agents pose in a surgical setting, and their preferences for the continued use of the agents during and after oculoplastic surgery. To obtain these data, the authors prospectively surveyed 129 patients who had an oculoplastic surgery clinical evaluation at our tertiary care academic facility. Because no previously validated questionnaire on this topic existed, the authors utilized a novel questionnaire the authors developed. For antithrombotic medications, about 60% of patients felt there were risks associated both with stopping and continuing the agent during surgery. For antithrombotic supplements, more patients answered there were risks associated with continuing the agents during surgery versus stopping the agents during surgery (40% versus 25%, respectively). There was a relationship between patients’ knowledge that they were on an antithrombotic prescription and their understanding of the risks associated with antithrombotic usage during surgery as well as sudden discontinuation of the prescription. With an understanding of the patient’s point of view, surgeons will be equipped to have multifaceted conversations with their patients surrounding their medications, systemic health, and oculoplastic surgery.
Transanal Hemorrhoidal Dearterialization with Mucopexy Versus Ferguson Hemorrhoidectomy for Prolapsed Internal Hemorrhoids
Authors: Gachabayov Mahir , Angelos George , Orangio Guy , Abcarian Herand , Bergamaschi Roberto ,   Hemorrhoids Study Group
Published: June 2023

Objective:

To compare transanal hemorrhoidal dearterialization (THD) with mucopexy to Ferguson hemorrhoidectomy in terms of recurrence rates and quality of life.

Background:

There is uncertainty regarding the durability of the therapeutic effect of THD with mucopexy compared to Ferguson hemorrhoidectomy in terms of recurrence rates.

Methods:

This was a multicenter prospective study. Participating surgeons performed the operation they knew best enrolling 10 patients each. Surgeons’ unedited videos were reviewed by an independent expert. Patients with prolapsed internal hemorrhoids in at least three columns were eligible. The primary endpoint was recurrence rates defined as prolapsing internal hemorrhoids. Patient-reported outcomes and satisfaction were evaluated with Pain Scale and Brief Pain Inventory, Fecal Incontinence Quality Of Life (FIQOL), Cleveland Clinic Incontinence, Constipation, Short-Form 12 (SF-12) scores and Patient satisfaction (4-point Likert) scale.

Results:

Twenty surgeons enrolled 197 patients. THD patients had lower Visual pain scores at POD1 (6.2 vs. 8.3, P=0.047), POD7 (4.5 vs. 7.7, P=0.021), POD14 (2.8 vs. 5.3, P<0.001) and medication use at POD14 (23% vs. 58%, P<0.001). Median follow-up was 3.1 (1.0–5.5) years. Recurrence rates did not differ between the study arms (5.9% vs. 2.4%, P=0.253). Patient satisfaction rate was higher after THD at POD14 (76.4% vs. 52.5%, P=0.031) and 3 months (95.1% vs. 63.3%, P=0.029), but did not differ at 6 months (91.7% vs. 88%, P=0.228) and 1 year (94.2% vs. 88%, P=0.836).

Conclusion:

THD with mucopexy was associated with improved patient-reported outcomes and quality of life as compared to Ferguson hemorrhoidectomy with non-significantly different recurrence rates.
The A domain of clonal complex 1-type fibronectin binding protein B promotes adherence and biofilm formation in Staphylococcus aureus
Authors: Henderson Sara R. , Geoghegan Joan A.
Published: June 2023

Adhesive interactions between

Staphylococcus aureus

and the host rely on cell-wall-anchored proteins such as fibronectin-binding protein B (FnBPB). Recently we showed that the FnBPB protein expressed by clonal complex (CC) 1 isolates of

S. aureus

mediates bacterial adhesion to corneodesmosin. The proposed ligand-binding region of CC1-type FnBPB shares just 60 % amino acid identity with the archetypal FnBPB protein from CC8. Here we investigated ligand binding and biofilm formation by CC1-type FnBPB. We found that the A domain of FnBPB binds to fibrinogen and corneodesmosin and identified residues within the hydrophobic ligand trench in the A domain that are essential for the binding of CC1-type FnBPB to ligands and during biofilm formation. We further investigated the interplay between different ligands and the influence of ligand binding on biofilm formation. Overall, our study provides new insights into the requirements for CC1-type FnBPB-mediated adhesion to host proteins and FnBPB-mediated biofilm formation in

S. aureus

.
Predictors and outcomes of Cardiac Dyssynchrony among patients with heart failure attending Benjamin Mkapa Hospital in Dodoma, central Tanzania: A protocol of prospective-longitudinal study
Authors: Bilikundi Patrick , Alphonce Baraka , Nyundo Azan , Meda John
Published: June 2023

Introduction

Cardiac Dyssynchrony is prevalent among patients with heart failure with high cost of care and potentially poor outcomes. Nevertheless, little is known about cardiac dyssynchrony among heart failure patients, especially in developing countries. This study aims at assessing the predictors and outcomes of cardiac dyssynchrony among heart failure patients attending the cardiology department at Benjamin Mkapa Referral Hospital in Dodoma, central Tanzania

Methods

The study will follow a prospective longitudinal design involving participants aged 18yrs and above with heart failure attending the Cardiology Department at Benjamin Mkapa Hospital. Heart failure will be identified based on Framingham’s score and patients will be enrolled and followed up for six months. Baseline socio-demographic and clinical characteristics will be taken during enrollment. Outcomes of interest at six months include worsening of heart failure, readmission and death. Continuous data will be summarized as Mean (SD) or Median (IQR), and categorical data will be summarized using proportions and frequencies. Binary logistic regression will be used to determine predictors and outcomes of Cardiac Dyssynchrony among patients with heart failure.
Direct interhemispheric cortical communication via thalamic commissures: a new white-matter pathway in the primate brain
Authors: Szczupak Diego , Schaeffer David J. , Tian Xiaoguang , Choi Sang-Ho , Fang-Cheng  , Iack Pamela Meneses , Campos Vinicius P. , Mayo J. Patrick , Patsch Janina , Mitter Christian , Haboosheh Amit , Vieira Marcelo A.C. , Kasprian Gregor , Tovar-Moll Fernanda , Lent Roberto , Silva Afonso C.
Published: June 2023

Cortical neurons of eutherian mammals project to the contralateral hemisphere, crossing the midline primarily via the corpus callosum and the anterior, posterior, and hippocampal commissures. We recently reported an additional commissural pathway in rodents, termed the thalamic commissures (TCs), as another interhemispheric axonal fiber pathway that connects cortex to the contralateral thalamus. Here, we demonstrate that TCs also exist in primates and characterize the connectivity of these pathways with high-resolution diffusion-weighted magnetic resonance imaging, viral axonal tracing, and functional MRI. We present evidence of TCs in both New World (Callithrix jacchusandCebus apella) and Old World primates (Macaca mulatta). Further, like rodents, we show that the TCs in primates develop during the embryonic period, forming anatomical and functionally active connections of the cortex with the contralateral thalamus. We also searched for TCs in the human brain, showing their presence in humans with brain malformations, although we could not identify TCs in healthy subjects. These results pose the TCs as an important fiber pathway in the primate brain, allowing for more robust interhemispheric connectivity and synchrony and serving as an alternative commissural route in developmental brain malformations.

Significance statement

Brain connectivity is a central topic in neuroscience. Understanding how brain areas can communicate allows for the comprehension of brain structure and function. We have described in rodents a new commissure pathway that connects the cortex to the contralateral thalamus. Here, we investigate whether this pathway exists in non-human primates and humans. The presence of these commissures poses the TCs as an important fiber pathway in the primate brain, allowing for more robust interhemispheric connectivity and synchrony and serving as an alternative commissural route in developmental brain malformations.
Localization of PPM1H phosphatase tunes Parkinson’s disease-linked LRRK2 kinase-mediated Rab GTPase phosphorylation and ciliogenesis
Authors: Yeshaw Wondwossen M. , Adhikari Ayan , Chiang Claire Y. , Dhekne Herschel S. , Wawro Paulina S. , Pfeffer Suzanne R.
Published: June 2023

PPM1H phosphatase reverses Parkinson’s disease-associated, LRRK2-mediated Rab GTPase phosphorylation. We show here that PPM1H relies on an N-terminal amphipathic helix for Golgi localization. The amphipathic helix enables PPM1H to bind to liposomes in vitro, and small, highly curved liposomes stimulate PPM1H activity. We artificially anchored PPM1H to the Golgi, mitochondria, or mother centriole. Our data show that regulation of Rab10 GTPase phosphorylation requires PPM1H access to Rab10 at or near the mother centriole. Moreover, poor co-localization of Rab12 explains in part why it is a poor substrate for PPM1H in cells but not in vitro. These data support a model in which localization drives PPM1H substrate selection and centriolar PPM1H is critical for regulation of Rab GTPase-regulated ciliogenesis. Moreover, Golgi localized PPM1H maintains active Rab GTPases on the Golgi to carry out their non-ciliogenesis-related functions in membrane trafficking.

Significance Statement

Pathogenic, hyperactive LRRK2 kinase is strongly linked to Parkinson’s disease and LRRK2 phosphorylates a subset of Rab GTPases that are master regulators of membrane trafficking. PPM1H phosphatase specifically dephosphorylates Rab8A and Rab10, the major LRRK2 substrates. Here we provide novel cell biological and biochemical insight related to the localization and activation of PPM1H phosphatase. Understanding how PPM1H modulates LRRK2 activity is of fundamental interest and also important, as activators of PPM1H may eventually benefit Parkinson’s disease patients.
A novel 4D fMRI clustering technique to examine event-related spatiotemporal dynamics of face processing in naturalistic stimuli
Authors: Ekstrand C.
Published: June 2023

Cortical function is complex, nuanced, and involves information processing in a multimodal and dynamic world. However, previous functional magnetic resonance imaging (fMRI) research has generally characterized static activation differences between strictly controlled proxies of real-world stimuli that do not encapsulate the complexity of everyday multimodal experiences. Of primary importance to the field of neuroimaging is the development of techniques that distill complex spatiotemporal information into simple, behaviorally relevant representations of neural activation. Herein, we present a novel 4D spatiotemporal clustering method to examine dynamic neural activity associated with events (specifically the onset of human faces in audiovisual movies). Results from this study showed that 4D spatiotemporal clustering can extract clusters of fMRI activation over time that closely resemble the known spatiotemporal pattern of human face processing without the need to model a hemodynamic response function. Overall, this technique provides a new and exciting window into dynamic functional processing across both space and time using fMRI that has wide applications across the field of neuroscience.
Secondary structures that regulate mRNA translation provide insights for ASO-mediated modulation of cardiac hypertrophy
Authors: Hedaya Omar M. , Subbaiah Kadiam C. Venkata , Jiang Feng , Xie Li Huitong , Wu Jiangbin , Khor EngSoon , Zhu Mingyi , Mathews David H. , Proschel Chris , Yao Peng
Published: June 2023

Translation of upstream open reading frames (uORFs) typically abrogates translation of main (m)ORFs. The molecular mechanism of uORF regulation in cells is not well understood. Here, we identified a double-stranded RNA (dsRNA) structure residing within theGATA4uORF that augments uORF translation and inhibits mORF translation. Antisense oligonucleotides (ASOs) that disrupt this dsRNA structure promote mORF translation, while ASOs that base-pair immediately downstream (i.e., forming a bimolecular double-stranded region) of either the uORF or mORF start codon enhance uORF or mORF translation, respectively. Human cardiomyocytes and mice treated with a uORF-enhancing ASO showed reduced cardiac GATA4 protein levels and increased resistance to cardiomyocyte hypertrophy. We further show the general utility of uORF-dsRNA- or mORF- targeting ASO to regulate mORF translation for other mRNAs. Our work demonstrates a regulatory paradigm that controls translational efficiency and a useful strategy to alter protein expression and cellular phenotypes by targeting or generating dsRNA downstream of a uORF or mORF start codon.

Bullet points for discoveries

dsRNA withinGATA4uORF activates uORF translation and inhibits mORF translation.

ASOs that target the dsRNA can either inhibit or enhanceGATA4mORF translation.

ASOs can be used to impede hypertrophy in human cardiomyocytes and mouse hearts.

uORF- and mORF-targeting ASOs can be used to control translation of multiple mRNAs.
Assumptions for creating matrices of evidence to estimate overlap of primary studies in overviews of reviews: Protocol for a meta-research study
Authors: Bracchiglione Javier , Meza Nicolás , Lunny Carole , Pieper Dawid , Madrid Eva , Urrútia Gerard , Bonfill Cosp Xavier
Published: June 2023

Introduction

Overlap of primary studies among systematic reviews (SRs) included in an overview is a major challenge, as it may bias results or artificially increase the precision of the synthesis. Matrices of evidence and corrected covered area (CCA) calculation are recommended methods to manage overlap, but there is little guidance on how to construct these matrices. This research aims to explore variations in the estimation of overlap using CCA matrices under different assumptions.

Methods

We will include overviews published in 2023. We will describe the methods used by authors to deal with overlap, and we will calculate a summary CCA (a CCA for the whole matrix of evidence) and a pairwise CCA (a CCA for each possible pair of included SRs), comparing the results under different assumptions that may modify the evidence matrix and thus the CCA. These assumptions include: publication-thread adjustments (i.e. the consideration of each set of references regarding a single primary study as a unique row in a matrix of evidence), scope adjustments (i.e. the consideration only of the SRs and primary studies providing useful data for a given outcome within an overview) and chronological structural missingness adjustments (i.e. the exclusion of primary studies published after a given SR for purposes of CCA calculation). We will assess overlap at an overview and outcome level.

Discussion

We propose clear definitions for the key assumptions for creating matrices of evidence. We expect to provide a guide for overview authors to better interpret their CCA estimations.

Article Summary

Strengths and limitations of this study

This protocol explores the assumptions underlying the overlap assessment in overviews of systematic reviews, that so far have not been explicitly addressed.

These assumptions include scope adjustments, publication-thread adjustments, structural missingness adjustments, and analysis at an overview or outcome level.

We provide clear definitions for key overlap concepts that will guide authors for making their overlap assessments more explicit when using a matrix of evidence or corrected covered area approach.

We plan to conduct exploratory analyses under different assumptions in a purposive sample of overview, hence, we will not comprehensively include all the overviews in the study period.

We will conduct all the analysis calculating the corrected covered area for the whole matrices (overall approach) and for every possible pair of systematic reviews within each matrix (pairwise approach).
A small molecule inhibitor of PTP1B and PTPN2 enhances T cell anti-tumor immunity
Authors: Liang Shuwei , Tran Eric , Du Xin , Dong Jiajun , Sudholz Harrison , Chen Hao , Qu Zihan , Huntington Nicholas D. , Babon Jeffrey J. , Kershaw Nadia J. , Zhang Zhong-Yin , Baell Jonathan B. , Wiede Florian , Tiganis Tony
Published: June 2023

The inhibition of protein tyrosine phosphatases 1B (PTP1B) and N2 (PTPN2) has emerged as an exciting approach for bolstering T cell anti-tumor immunity. ABBV-CLS-484 is a PTP1B/PTPN2 inhibitor in clinical trials for solid tumors. Here we have explored the therapeutic potential of a related small-molecule-inhibitor, Compound-182. We demonstrate that Compound-182 is a highly potent and selective active site competitive inhibitor of PTP1B and PTPN2 that enhances T cell recruitment and activation and represses the growth of tumors in mice, without promoting overt immune-related toxicities. The enhanced anti-tumor immunity in immunogenic tumors could be ascribed to the inhibition of PTP1B/PTPN2 in T cells, whereas in cold tumors, Compound-182 elicited direct effects on both tumor cells and T cells. Importantly, treatment with Compound-182 rendered otherwise resistant tumors sensitive to α-PD1 therapy. Our findings establish the potential for small molecule inhibitors of PTP1B and PTPN2 to enhance anti-tumor immunity and combat cancer.
Measuring lattices
Authors: Andrews Lawrence C. , Bernstein Herbert J.
Published: June 2023

Unit cells are used to represent crystallographic lattices. Calculations measuring the differences between unit cells are used to provide metrics for measuring meaningful distances between three-dimensional crystallographic lattices. This is a surprisingly complex and computationally demanding problem. A review is presented of the current best practice using Delaunay-reduced unit cells in the six-dimensional real space of Selling scalar cells S
6 and the equivalent three-dimensional complex space C
3. The process is a simplified version of the process needed when working with the more complex six-dimensional real space of Niggli-reduced unit cells G
6. Obtaining a distance begins with identification of the fundamental region in the space, continues with conversion to primitive cells and reduction, analysis of distances to the boundaries of the fundamental unit, and is completed by a comparison of direct paths with boundary-interrupted paths, looking for a path of minimal length.
Global brands or local heroes? A comparative study of Egyptian consumer perceptions and behaviors in the fashion and apparel industry
Authors: Boseila Iman , Mahrous Abeer A. , Abouaish Ehab
Published: June 2023

Purpose

The paper examined the impact of brand-identity expressiveness and perceived brand value that was neglected in prior literature, in addition to perceived brand quality and prestige, on behavioral intention. Research also tests if certain consumer values moderate this relationship.

Design/methodology/approach

Mall-interception technique was used. Also, partial least square-structural equation modelling (PLS-SEM) was used to analyze data and test research hypotheses.

Findings

Results indicate that perceived brand globalness (PBG) and perceived brand localness (PBL) are significantly positively associated with perceived quality and prestige. Besides, the inclusion of brand-identity expressiveness and perceived brand value was supported. PBL showed a greater association with brand identity expressiveness compared to PBG, different from previous findings. Furthermore, the total indirect effect of PBG on behavioral intentions was significant through the routes of perceived quality and prestige, compared to a weak and non-significant effect for PBL through the quality route.

Originality/value

This study proposes a comprehensive model testing additional pathways through which global and local brands can boost their preferences.
Developing a multidimensional performance measurement framework for international construction joint ventures (ICJVs): the perspective of Ghana-hosted ICJVs' practitioners
Authors: Tetteh Mershack Opoku , Chan Albert P.C. , Darko Amos , Özorhon Beliz , Adinyira Emmanuel
Published: June 2023

Purpose

International construction joint ventures (ICJVs) will fully realize their potential for success and effectively monitor performance when an adequate and suitable performance benchmark is established. However, existing studies fall short of adequately providing a mutually acceptable benchmark for assessing the performance of ICJVs. This study aims to develop an adequate and suitable performance measurement framework for ICJVs.

Design/methodology/approach

A twofold structured questionnaire survey, supplemented by semi-structured interviews, was used to collect data from the practitioners of ICJVs hosted in the developing country of Ghana. The data were analyzed by using descriptive statistics, confirmatory factor analysis (CFA) and a hybrid-fuzzy logic approach.

Findings

A list of 30 performance indicators (PIs), defined by project performance, perceived satisfaction, company/partner performance, socio-environmental performance and performance of ICJV management, was validated and proved to be significant. Only 22 out of the 30 PIs, focusing on project efficiency, societal improvement and organizational goals are realized by the ICJV practitioners. Further, suitable determinants and viable quantitative ranges for measuring each PI are established to prevent different interpretations of the meanings of PIs and objectively express the level of success in quantitative terms. The results call for further investigation of the convergence between the practice of and research into some PIs (e.g. socio-environmental performance) and a range of different performance levels (PLs) in a more scientific manner.

Practical implications

This study not only advances the knowledge base and practice of performance measurement in ICJVs but could also assist stakeholders and decision-makers to assess, compare and monitor the performance of different ICJV projects on common grounds objectively.

Originality/value

This study not only comprehensively assessed PIs – what to measure – but also systematically determined suitable determinants – how to measure – for each PI.
The long-run impact of remittances on house prices in Kenya
Authors: Chege Fredrick , Gholipour Hassan F. , Yam Sharon
Published: June 2023

Purpose

Given the coincidental and sustained rise in house prices and foreign capital flows in Kenya, this study aims to understand whether a long-run relationship exists between real diaspora remittances and real house prices.

Design/methodology/approach

This study uses data from 2004-Q1 to 2020-Q4 and applies an autoregressive distributed lag model for estimation.

Findings

The results indicate that a positive and significant relationship exists between real remittances and real house prices in Kenya in the long run.

Originality/value

To the best of the authors’ knowledge, there is no study exploring the relationship between real remittance inflows and house prices in Kenya, after controlling for other key macroeconomic determinants of house prices. This study addresses this research gap.
Does urban tourism development impact urban housing prices?
Authors: Cong Shufeng , Chin Lee , Abdul Samad Abdul Rahim
Published: June 2023

Purpose

The purpose of this study is to investigate the relationship between tourism development and urban housing prices in Chinese cities. Specifically, the study aimed to explore whether there is a relationship between the two variables in tourist and non-tourist cities and whether there is a non-linear relationship between them.

Design/methodology/approach

In this study, the entropy method was used to construct the China City Tourism Development Index, which provides a more comprehensive measure of the level of tourism development in different cities. In total, 45 major cities in China were studied using the panel data approach for the period of 2011 to 2019.

Findings

The empirical analysis conducted for this study found that tourism development affects urban house prices, and that there is an inverted U-shaped relationship. However, this varies across cities, with house prices in tourist cities tending to be more influenced by tourism development than non-tourist cities. Also, foreign direct investment, population size, fixed asset investment and disposable income per capita were found to have an impact on house prices in both tourism and non-tourism cities.

Originality/value

There are significant differences in tourism development and urban house prices in different cities in China. This study considers these differences when examining the impact of tourism on house prices in 45 major cities in China by dividing the sample cities into tourist and non-tourist cities.
Improvement of supplier delivery performance under uncertain capacity allocation and delivery time window
Authors: Sakhare Chirag Suresh , Chakraborty Sayan , Sarmah Sarada Prasad , Singh Vijay
Published: June 2023

Purpose

Original equipment manufacturers and other manufacturing companies rely on the delivery performance of their upstream suppliers to maintain a steady production process. However, supplier capacity uncertainty and delayed delivery often poses a major concern to manufacturers to carry out their production plan as per the desired schedules. The purpose of this paper is to develop a decision model that can improve the delivery performance of suppliers to minimise fluctuations in the supply quantity and the delivery time and thus maximising the performance of the supply chain.

Design/methodology/approach

The authors studied a single manufacturer – single supplier supply chain considering supplier uncertain capacity allocation and uncertain time of delivery. Mathematical models are developed to capture expected profit of manufacturer and supplier under this uncertain allocation and delivery behaviour of supplier. A reward–penalty mechanism is proposed to minimise delivery quantity and time of delivery fluctuations from the supplier. Further, an order-fulfilment heuristic based on delivery probability is developed to modify the order quantity which can maximise the probability of a successful deliveries from the supplier.

Findings

Analytical results reveal that the proposed reward–penalty mechanism improves the supplier delivery consistency. This consistent delivery performance helps the manufacturer to maintain a steady production schedule and high market share. Modified ordering schedule developed using proposed probability-based heuristic improves the success probability of delivery from the supplier.

Practical implications

Practitioners can benefit from the findings of this study to comprehend how contracts and ordering policy can improve the supplier delivery performance in a manufacturing supply chain.

Originality/value

This paper improves the supplier delivery performance considering both the uncertain capacity allocation and uncertain time of delivery.
Three lines model paradigm shift: a blockchain-based control framework
Authors: Brender Nathalie , Gauthier Marion , Morin Jean-Henry , Salihi Arber
Published: June 2023

Purpose

While the three lines model (TLM) provides an organizational structure to execute risk and control duties, research and practice show limitations in the model's implementation. These limitations result in governance issues. Such issues, together with control weaknesses, could be addressed by leveraging properties of distribution, transparency, and immutability of blockchain technology. To this end, in this paper the authors propose a conceptual control framework based on blockchain technology to augment control practice.

Design/methodology/approach

The design of the resulting blockchain-based control framework (BBCF) and its prototype, based on the design science research methodology (DSRM), is presented and discussed in terms of the potential impact in the context of the identified problems within the TLM.

Findings

One potential outcome of BBCF could be to redefine the scope and boundaries of some of the activities in audit and control practices from a more static to a more dynamic and prospective role. In a larger context of improving governance practices, the BBCF could set the path for a more inclusive and participatory interaction between the different governance actors of an organization.

Research limitations/implications

However, this assumes that blockchain is more widely adopted despite its complexity and rigidity.

Practical implications

BBCF covering both a conceptual model design and a reference implementation provides an innovation in audit and control. BBCF could include all relevant stakeholders who have an interest in corporate governance and control activities, including the regulators.

Originality/value

The contribution intends to serve both as a starting point for discussing the evolution of audit and control practice based on blockchain technology, as well as an initial actionable prototype for experimentation and further development.