bluuebunny/crossref_metadata_2025 huggingface dataset:
Systemic Sarcoidosis Presenting in a Scar
Authors: Xiao Amy , Falcone Lauryn M. , English III Joseph C.
Published: January 2023

While most forms of sarcoidosis of the skin do not require treatment, 40% of patients initially diagnosed with cutaneous sarcoidosis are found to have an asymptomatic disease involving other organ systems. It is the involvement of the lungs, heart, eyes, and nervous system which most often contributes to morbidity/mortality. An early and accurate diagnosis of sarcoidosis is difficult because patients may be asymptomatic, initial presentations may vary, and there is no single reliable diagnostic test except biopsy. We present a case of scar sarcoidosis which led to the diagnosis of stage II pulmonary sarcoidosis in a woman in her 50s. Her scar sarcoidosis presented as well-circumscribed, reddish-brown macules surrounding an atrophic scar from a prior skin graft on the right leg. Biopsy revealed scattered, well-formed, non-necrotizing granulomas of the dermis composed of epithelioid histiocytes and multinucleated giant cells, surrounded by a sparse infiltrate of lymphocytes and histiocytes. A CT chest demonstrated extensive hilar lymphadenopathy, leading to a diagnosis of stage II pulmonary sarcoidosis with cutaneous involvement. This case illustrates the interesting presentation of scar sarcoidosis and underscores the importance of a broad differential including sarcoidosis for skin changes around scars and underscores the need for early biopsy. Prompt cutaneous diagnosis leads to earlier systemic evaluation, therapeutics, and better outcomes.
Predicting COVID-19 Pandemic Endpoint in Some Sub-Saharan African and European Countries
Authors: Akuamoah Saviour Worlanyo , Ayimah John Coker , Yaro David , Krampa Elikem Kofi , Danso Awura Amma Adomaa
Published: January 2023

In this study, a novel modified SIR model is presented with two control measures to predict the endpoint of COVID-19, in top three sub-Saharan African countries (South Africa, Ethiopia, and Kenya) including Ghana and top four European countries (France, Germany, UK, and Italy). The reproduction number’s sensitivity indices with regard to the model parameters were explicitly derived and then numerically evaluated. Numerical simulations of the suggested optimal control schemes in general showed a continuous result of decline at different anticipated extinction timelines. Another interesting observation was that in the simulation of sub-Saharan African dynamics, it was observed that the use of personal protective equipment was more effective than the use of vaccination, whereas in Europe, the use of vaccination was more effective than personal protective equipment. From the simulations, the conclusion is that COVID-19 will end before the 3rd year in Ghana, before the 6th year in Kenya, and before the 9th year in both Ethiopia and South Africa.
Effect of Proprietary Chinese Medicine on Coronary Microvascular Dysfunction in Patients with Microvascular Angina: A Systematic Review and Meta‐Analysis
Authors: Yu Qiuyu , Xu Xiaoyu , Wang Shun , Fan Yu , Zhang Jian , Leng Yingshu , Liu Fuming
Published: January 2023

Background. Microvascular angina (MVA) has received increasing attention and interest in recent years, but there are still some shortcomings in the diagnosis and treatments at current stage. In recent years, several studies have confirmed the efficacy of proprietary Chinese medicines (PCMs) in improving MVA symptoms; however, there is no systematic review and meta‐analysis to comprehensively assess the efficacy of PCMs in this area. Objective. Investigating the clinical efficacy of proprietary Chinese medicines for treating MVA and coronary microvascular function. Methods. We looked up articles from January 1, 2012, to the present from eight databases. Then, we screened the literature and followed the 2019 version 2 of Cochrane risk of bias tool for systematic review. The Stata/SE 15.0 software was used for the meta‐analysis. Results. There are 21 studies, including 1,641 patients who were included in this review. According to the results, the combination of PCMs and conventional MVA treatment was able to further enhance clinical efficacy [RR = 1.28, 95% CI (1.20, 1.36), p < 0.001], prolong the time of duration on the treadmill exercise testing (TET) [SMD = 1.49, 95% CI (0.63, 2.36), p = 0.001] and improve levels of NO [SMD = −1.77 95% CI (−2.11, −1.43), p < 0.001]. At the same time, PCMs could also decrease the microvascular resistance index (IMR) [SMD = −1.79, 95% CI (−2.58, −1.00), p < 0.001)], serum level of hs‐CRP [SMD = −1.21, 95% CI (−1.84, −0.58), p < 0.001] and ET‐1 [SMD = −1.77 95% CI (−2.11, −1.43), p < 0.001]. Regards to medication safety, a total of 27 adverse events occurred, including 10 cases in the intervention group and 17 cases in the control group. Conclusion. The study suggests that the combination of PCMs and conventional MVA treatment enhances clinical efficacy and could better improve coronary microvascular function. In the future, we expect more high‐quality, randomized, double‐blind clinical studies to validate the safety, and efficacy of PCMs to provide valuable evidence‐based medicine (EBM) for the treatment of MVA with PCMs.
Zinc Finger MYND-Type Containing 8 (ZMYND8) Is Epigenetically Regulated in Mutant Isocitrate Dehydrogenase 1 (IDH1) Glioma to Promote Radioresistance
Authors: Carney Stephen V. , Banerjee Kaushik , Mujeeb Anzar , Zhu Brandon , Haase Santiago , Varela Maria L. , Kadiyala Padma , Tronrud Claire E. , Zhu Ziwen , Mukherji Devarshi , Gorla Preethi , Sun Yilun , Tagett Rebecca , Núñez Felipe J. , Luo Maowu , Luo Weibo , Ljungman Mats , Liu Yayuan , Xia Ziyun , Schwendeman Anna , Qin Tingting , Sartor Maureen A. , Costello Joseph F. , Cahill Daniel P. , Lowenstein Pedro R. , Castro Maria G.
Published: January 2023

Purpose:

Mutant isocitrate dehydrogenase 1 (mIDH1) alters the epigenetic regulation of chromatin, leading to a hypermethylation phenotype in adult glioma. This work focuses on identifying gene targets epigenetically dysregulated by mIDH1 to confer therapeutic resistance to ionizing radiation (IR).

Experimental Design:

We evaluated changes in the transcriptome and epigenome in a radioresistant mIDH1 patient-derived glioma cell culture (GCC) following treatment with an mIDH1-specific inhibitor, AGI-5198. We identified Zinc Finger MYND-Type Containing 8 (ZMYND8) as a potential target of mIDH1 reprogramming. We suppressed ZMYND8 expression by shRNA knockdown and genetic knockout (KO) in mIDH1 glioma cells and then assessed cellular viability to IR. We assessed the sensitivity of mIDH1 GCCS to pharmacologic inhibition of ZMYND8-interacting partners: HDAC, BRD4, and PARP.

Results:

Inhibition of mIDH1 leads to an upregulation of gene networks involved in replication stress. We found that the expression of ZMYND8, a regulator of DNA damage response, was decreased in three patient-derived mIDH1 GCCs after treatment with AGI-5198. Knockdown of ZMYND8 expression sensitized mIDH1 GCCs to radiotherapy marked by decreased cellular viability. Following IR, mIDH1 glioma cells with ZMYND8 KO exhibit significant phosphorylation of ATM and sustained γH2AX activation. ZMYND8 KO mIDH1 GCCs were further responsive to IR when treated with either BRD4 or HDAC inhibitors. PARP inhibition further enhanced the efficacy of radiotherapy in ZMYND8 KO mIDH1 glioma cells.

Conclusions:

These findings indicate the impact of ZMYND8 in the maintenance of genomic integrity and repair of IR-induced DNA damage in mIDH1 glioma.

See related commentary by Sachdev et al., p. 1648
Allogeneic CAR T Cells Targeting DLL3 Are Efficacious and Safe in Preclinical Models of Small Cell Lung Cancer
Authors: Zhang Yi , Tacheva-Grigorova Silvia K. , Sutton Janette , Melton Zea , Mak Yvonne S.L. , Lay Cecilia , Smith Bryan A. , Sai Tao , Van Blarcom Thomas , Sasu Barbra J. , Panowski Siler H.
Published: January 2023

Purpose:

Small cell lung cancer (SCLC) is an aggressive disease with limited treatment options. Delta-like ligand 3 (DLL3) is highly expressed on SCLC and several other types of neuroendocrine cancers, with limited normal tissue RNA expression in brain, pituitary, and testis, making it a promising CAR T-cell target for SCLC and other solid tumor indications.

Experimental Design:

A large panel of anti-DLL3 scFv-based CARs were characterized for both in vitro and in vivo activity. To understand the potential for pituitary and brain toxicity, subcutaneous or intracranial tumors expressing DLL3 were implanted in mice and treated with mouse cross-reactive DLL3 CAR T cells.

Results:

A subset of CARs demonstrated high sensitivity for targets with low DLL3 density and long-term killing potential in vitro. Infusion of DLL3 CAR T cells led to robust antitumor efficacy, including complete responses, in subcutaneous and systemic SCLC in vivo models. CAR T-cell infiltration into intermediate and posterior pituitary was detected, but no tissue damage in brain or pituitary was observed, and the hormone-secretion function of the pituitary was not ablated.

Conclusions:

In summary, the preclinical efficacy and safety data presented here support further evaluation of DLL3 CAR T cells as potential clinical candidates for the treatment of SCLC.
Much Ado about ASPS: The Rapidly Changing Treatment Paradigms of 2022
Authors: Wilky Breelyn A. , Maleddu Alessandra
Published: January 2023

A recent randomized phase II study of sunitinib or cediranib in alveolar soft part sarcoma established benchmark activity for commonly used tyrosine kinase inhibitors (TKI). The impact of TKIs, as well as immunotherapy, has redefined treatment paradigms and greatly improved outcomes for this historically dismal sarcoma.

See related article by Nguyen et al., p. 1200
Contrast-Enhanced Ultrasound Liver Imaging Reporting and Data System in Hepatocellular Carcinoma ≤5 cm: Biological Characteristics and Patient Outcomes
Authors: Cai Wen-Jia , Ying Minghua , Zheng Rong-Qin , Liao Jintang , Luo Baoming , Tang Lina , Cheng Wen , Yang Hong , Wei An , Yang Yilin , Wang Hui , Luo Yan-Chun , Liu Cun , Zhong Hui , Yang Qi , Yu Jie , Liang Ping
Published: January 2023

Introduction: The present study aimed to evaluate the influence of biological characteristics of hepatocellular carcinoma (HCC) on the Liver Imaging Reporting and Data System (LI-RADS) v2017 category of contrast-enhanced ultrasound (CEUS) in patients with high risk and compare the outcomes among different categories after radical resection. Methods: Between June 2017 and December 2020, standardized CEUS data of liver nodules were prospectively collected from multiple centers across China. We conducted a retrospective analysis of the prospectively collected data on HCCs measuring no more than 5 cm, as diagnosed by pathology. LI-RADS categories were assigned after thorough evaluation of CEUS features. Then, CEUS LI-RADS categories and major features were compared in different differentiation, Ki-67, and microvascular invasion (MVI) statuses. Differences in recurrence-free survival (RFS) among different LI-RADS categories were further analyzed. Results: A total of 293 HCC nodules in 293 patients were included. This study revealed significant differences in the CEUS LI-RADS category of HCCs among differentiation (p < 0.001) and levels of Ki-67 (p = 0.01) and that poor differentiation (32.7% in LR-M, 12% in LR-5, and 6.2% in LR-4) (p < 0.001) and high level of Ki-67 (median value 30%) were more frequently classified into the LR-M category, whereas well differentiation (37.5% in LR-4, 15.1% in LR-5, and 11.5% in LR-M) and low levels of Ki-67 (median value 11%) were more frequently classified into the LR-4 category. No significant differences were found between MVI and CEUS LI-RADS categories (p > 0.05). With a median follow-up of 23 months, HCCs assigned to different CEUS LI-RADS classes showed no significant differences in RFS after resection. Conclusions: Biological characteristics of HCC, including differentiation and level of Ki-67 expression, could influence major features of CEUS and impact the CEUS LI-RADS category. HCCs in different CEUS LI-RADS categories showed no significant differences in RFS after resection.
Design of wideband antenna using interdigital capacitance
Authors: Suriyan Kannadhasan , Venusamy Kanagaraj , Ponnuvel Indira Priya , Zakir Syed Khaja Ahmedudin , Alagarsamy Manjunathan
Published: January 2023

A pair of wideband antenna serve as an impedance transformer for the proposed antenna, which consists of a dipole with periodic capacitive loading. Periodic capacitive loading is achieved at each sector by adding interlaced coupling lines. In order to create a broad impedance bandwidth, the periodic interlaced coupling lines split each arm of the dipole into five portions. Currents are dispersed on the various sections at different frequencies. The suggested antenna is an excellent choice for radar applications since it has a high gain and a low amount of cross polarisation. With the aid of innovative design methods including codirectional inclusion of interdigital capacitance, this research study proposes an interdigital capacitance for wideband (WB) applications interdigital capacitor (IDC). The suggested IDC antenna, which works between 4.70 and 11 GHz, has dimensions of 6.36x6.35x1.6 mm3. This page explores in-depth data on gain over frequency, far field patterns, and surface current distribution on antennas. The suggested antenna's feasibility is shown by simulation data that demonstrates excellent equality on return loss.
Intrusion detection systems for internet of thing based big data: a review
Authors: Laassar Imane , Hadi Moulay Youssef
Published: January 2023

Network security is one of the foremost anxieties of the modern time. Over the previous years, numerous studies have been accompanied on the intrusion detection system. However, network security is one of the foremost apprehensions of the modern era this is due to the speedy development and substantial usage of altered technologies over the past period. The vulnerabilities of these technologies security have become a main dispute intrusion detection system is used to classify unapproved access and unusual attacks over the secured networks. For the implementation of intrusion detection system different approaches are used machine learning technique is one of them. In order to comprehend the present station of application of machine learning techniques for solving the intrusion discovery anomalies in internet of thing (IoT) based big data this review paper conducted. Total 55 papers are summarized from 2010 and 2021 which were centering on the manner of the single, hybrid and collaborative classifier design. This review paper also includes some of the basic information like IoT, big data, and machine learning approaches are discussed.
How Many Cases per Cluster? Operationalizing the Number of Units per Cluster Relative to Minimum Detectable Effects in Two-Level Cluster Randomized Evaluations with Linear Outcomes
Authors: Hedberg E. C.
Published: January 2023

In cluster randomized evaluations, a treatment or intervention is randomly assigned to a set of clusters each with constituent individual units of observations (e.g., student units that attend schools, which are assigned to treatment). One consideration of these designs is how many units are needed per cluster to achieve adequate statistical power. Typically, researchers state that “about 30 units per cluster” is the most that will yield benefit towards statistical precision. To avoid rules of thumb not grounded in statistical theory and practical considerations, and instead provide guidance for this question, the ratio of the minimum detectable effect size (MDES) to the larger MDES with one less unit per cluster is related to the key parameters of the cluster randomized design. Formulas for this subsequent difference effect size ratio (SDESR) at a given number of units are provided, as are formulas for finding the number of units for an assumed SDESR. In general, the point of diminishing returns occurs with smaller numbers of units for larger values of the intraclass correlation.
Beta-Lactamase-Producing Gram-Negative Bacterial Isolates Among the Patients Attending a Tertiary Care Hospital, Kathmandu, Nepal
Authors: Pariyar Manita , Adhikari Sanjib , Regmi Ramesh Sharma , Dhungel Binod , Banjara Megha Raj , Rijal Basista Prasad , Rijal Komal Raj , Ghimire Prakash
Published: January 2023

Over the times, carbapenems have been the choice of drug for treating multidrug-resistant (MDR) and extended spectrum beta-lactamase (ESBL)-producing organisms. The current study aimed at determining the occurrence of metallo beta-lactamase (MBL) and AmpC beta-lactamase (ABL) in gram negative bacteria isolated from clinical samples. A cross-sectional study was conducted amongst the patients visiting Manmohan Memorial Medical College and Teaching Hospital (MMTH), Kathmandu, Nepal from August 2017 to January 2018. A total of 4351 samples including urine, pus, wound swab, endotracheal tip, catheter tip, and blood were collected from the patients and processed by standard conventional microbiological methods. Antibiotic susceptibility testing (AST) of the isolates was performed by Kirby-Bauer disk diffusion method. Double disc synergy test was performed on carbapenem resistant organisms to detect production of MBL and inhibitor-based test was used for the detection of ABL production. Of the 4351 samples, 421 bacterial isolates belonging to 16 different genera were recovered, of which 303 (71.97%) were Gram negative bacilli (GNB). E. coli (189/303) and S. aureus (80/118) were the most prevalent among gram negatives and gram positives, respectively. Bacterial incidence was found significantly associated with gender, specimen type, and the department where the patients were enrolled. Colistin-sulfate and polymycin-B were the most effective drug against GNB, whereas imipenem against gram positives. Prevalence of MDR and methicillin-resistant S. aureus (MRSA) was 35.15% and 60%, respectively. The prevalence of MBL and ABL-producing isolate was 11(3.6%) and 13(4.3%), respectively. Pseudomonas aeruginosa (5/11) and E. coli (9/13) were the major MBL and ABL producers, respectively. MBL and ABL production was found to be significantly associated with the age of the patient and the specimen type. A regular antibiotic surveillance activity with screening for MBL and ABL-producing bacterial isolates in the hospital settings to curb the incidence and transmission of such difficult-to-treat pathogens.
Record of a dense succession of drowning phases in the Alpstein mountains, northeastern Switzerland: Part II—the Lower Cretaceous Schrattenkalk Formation (late Barremian)
Authors: Pictet Antoine , Tschanz Karl , Kürsteiner Peter
Published: January 2023

The Schrattenkalk Formation represents a complete succession of Lower Cretaceous shallow-water carbonate platform series cropping out in the Alpstein massif of north-eastern Switzerland. The Schrattenkalk Formation is traditionally divided into two sedimentary units, the “Lower” and the “Upper” Schrattenkalk, separated by the more marly Rawil Member. The “Lower” Schrattenkalk is habitually dated to the late Barremian, while the Rawil Member and the “Upper” Schrattenkalk are dated to the early Aptian. New field observations, however, call the lithostratigraphic dichotomy of the Schrattenkalk into question, as the neritic carbonates are disrupted by several key surfaces associated with karstic episodes and/or transgressive sediments, corresponding to ammonite-rich hemipelagic deposits on the distal shelf. A large number of ammonites were collected in the Drusberg Member as well as rare ammonites from the Schrattenkalk Formation. These ammonites as well as the neritic macrofauna from the Schrattenkalk Formation allow a precise dating of the onset of the Schrattenkalk Formation across the Alpstein massif and its successive phases of progradation. Three successive carbonate bodies and a fourth sedimentary intermediate rock body at the top of the Schrattenkalk platform are defined, based on new biostratigraphic data and updated interpretations of the sequence stratigraphy and geochemical data. The data shows a progressive onset of the Schrattenkalk carbonate platform along the studied transect, following a SE progradation over time. The oldest deposits refer to the upper Barremian T. vandenheckii Zone and the youngest carbonates to the uppermost Barremian M. sarasini Subzone. The new dating of the discontinuity surfaces and key-beds highlight three successive flooding events. The first drowning phase, which correlates with the "Sartousiana" event, dates from the middle late Barremian (upper T. vandenheckii—lower G. sartousiana Zone). The second phase, represented by the Rawil Member, is an incipient drowning, which seems to coincide with the latest Barremian Taxy event (usually reported to the I. giraudi and lowermost M. sarasini zones) according to rare ammonite discoveries. The final demise of the Schrattenkalk platform, situated close to the Barremian-Aptian boundary, is related to an exposure and consecutive drowning event.
Assessment of the influence of selected stress factors on the growth and survival of Listeria monocytogenes
Authors: Wiktorczyk-Kapischke Natalia , Skowron Krzysztof , Wałecka-Zacharska Ewa , Grudlewska-Buda Katarzyna , Wnuk Kacper , Buszko Katarzyna , Gospodarek-Komkowska Eugenia
Published: January 2023

Background

Listeria monocytogenesare Gram-positive rods, which are the etiological factor oflisteriosis.L. monocytogenesquickly adapts to changing environmental conditions. Since the main source of rods is food, its elimination from the production line is a priority. The study aimed to evaluate the influence of selected stress factors on the growth and survival ofL. monocytogenesstrains isolated from food products and clinical material.

Results

We distinguished fifty genetically different strains ofL. monocytogenes(PFGE method). Sixty-two percent of the tested strains represented 1/2a-3a serogroup. Sixty percent of the rods possessed ten examined virulence genes (fbpA,plcA,hlyA,plcB,inlB,actA,iap,inlA,mpl, prfA). Listeria Pathogenicity Island 1 (LIPI-1) was demonstrated among 38 (76.0%) strains. Majority (92.0%) of strains (46) were sensitive to all examined antibiotics. The most effective concentration of bacteriophage (inhibiting the growth of 22 strains; 44.0%) was 5 × 108PFU. In turn, the concentration of 8% of NaCl was enough to inhibit the growth of 31 strains (62.0%). The clinical strain tolerated the broadest pH range (3 to 10). Five strains survived the 60-min exposure to 70˚C, whereas all were alive at each time stage of the cold stress experiment. During the stress of cyclic freezing-defrosting, an increase in the number of bacteria was shown after the first cycle, and a decrease was only observed after cycle 3. The least sensitive to low nutrients content were strains isolated from frozen food. The high BHI concentration promoted the growth of all groups.

Conclusions

Data on survival in stress conditions can form the basis for one of the hypotheses explaining the formation of persistent strains. Such studies are also helpful for planning appropriate hygiene strategies within the food industry.
Effect of continuing the use of renin–angiotensin system inhibitors on mortality in patients hospitalized for coronavirus disease 2019: a systematic review, meta-analysis, and meta-regression analysis
Authors: Liu Qi , Fu Wei , Zhu Chang-ju , Ding Zi-heng , Dong Bin-bin , Sun Bao-qing , Chen Rong-chang
Published: January 2023

Background

The effect of angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) on mortality was preliminarily explored through the comparison of ACEIs/ARBs with non-ACEIs/ARBs in patients with coronavirus disease 2019 (COVID-19). Reaching a conclusion on whether previous ACEI/ARB treatment should be continued in view of the different ACE2 levels in the comparison groups was not unimpeachable. Therefore, this study aimed to further elucidate the effect of ACEI/ARB continuation on hospital mortality, intensive care unit (ICU) admission, and invasive mechanical ventilation (IMV) in the same patient population.

Methods

We searched PubMed, the Cochrane Library, Ovid, and Embase for relevant articles published between December 1, 2019 and April 30, 2022. Continuation of ACEI/ARB use after hospitalization due to COVID-19 was considered as an exposure and discontinuation of ACEI/ARB considered as a control. The primary outcome was hospital mortality, and the secondary outcomes included 30-day mortality, rate of ICU admission, IMV, and other clinical outcomes.

Results

Seven observational studies and four randomized controlled trials involving 2823 patients were included. The pooled hospital mortality in the continuation group (13.04%, 158/1212) was significantly lower than that (22.15%, 278/1255) in the discontinuation group (risk ratio [RR] = 0.45; 95% confidence interval [CI], 0.28–0.72; P = 0.001). Continuation of ACEI/ARB use was associated with lower rates of ICU admission (10.5% versus 16.2%, RR = 0.63; 95% CI 0.5–0.79; P < 0.0001) and IMV (8.2% versus 12.5%, RR = 0.62; 95% CI 0.46–0.83, P = 0.001). Nevertheless, the effect was mainly demonstrated in the observational study subgroup (P < 0.05). Continuing ACEI/ARB had no significant effect on 30-day mortality (P = 0.34), acute myocardial infarction (P = 0.08), heart failure (P = 0.82), and acute kidney injury after hospitalization (P = 0.98).

Conclusion

Previous ACEI/ARB treatment could be continued since it was associated with lower hospital deaths, ICU admission, and IMV in patients with COVID-19, although the benefits of continuing use were mainly shown in observational studies. More evidence from multicenter RCTs are still needed to increase the robustness of the data.

Trial registration PROSPERO (CRD42022341169). Registered 27 June 2022
Parkinsonism after ventriculoperitoneal shunt for hydrocephalus
Authors: Zhang Yue , Chen Bi W. , Mao Wei , Wu Feng Y. , Zhang Yan
Published: January 2023

Background

Parkinsonism after ventriculoperitoneal shunt in patients with hydrocephalus is a rare and profound complication that is often misdiagnosed, causing treatment to be delayed. To date, the characteristics of this disease have not been well described and summarized. Here, we report a rare case of parkinsonism after ventriculoperitoneal shunt; symptoms were aggravated by antipsychotic drugs but showed a good response to Madopar. Such cases have rarely been reported previously.

Case presentation

A 44-year-old man presented with parkinsonism, bilateral pyramidal tract signs, and oculomotor impairment four years after a successful ventriculoperitoneal shunt for idiopathic aqueduct stenosis resulting in obstructive hydrocephalus. Brain magnetic resonance imaging and computed tomography showed fluctuations in the lateral ventricle and the third ventricle without any intervention. The patient’s condition was aggravated by antipsychotic drugs but showed a good response to Madopar.

Conclusion

This observation suggests that parkinsonism in this patient was caused by reversible dysfunction of the presynaptic nigrostriatal dopaminergic pathway due to fluctuations in the lateral ventricle, representing the first hit to the dopaminergic signalling pathway, and antipsychotic drugs had an antagonistic effect on dopamine D2 receptors, representing the second hit. In addition, we summarize the pathophysiological mechanisms, clinical manifestations, treatments, and prognoses of this complication in 38 patients who met the inclusion criteria in 24 previous studies to increase neurologists’ understanding of the disease.
Risk of seizures in a population of women with BRCA-positive metastatic breast cancer from an electronic health record database in the United States
Authors: Liede Alexander , Sebby Wendy , Miriyala Ashok Kumar Reddy , Potluri Ravi , Mazumder Debasish , Ghosh Anirban , Papademetriou Eros , Kilpatrick Ryan , Tyczynski Jerzy E.
Published: January 2023

Background

Incidence and risk factors for seizures among women with advanced breast cancer (BC) and brain metastases are not well characterized across treatment-related or clinical subtypes. This study leveraged a large real-world dataset to describe incidence and risk factors for seizures in BRCA-associated metastatic breast cancer.

Methods

The Optum® de-identified electronic health records database was used. Females with a BC diagnoses between 2008 and 2018, with clinic visits 12 months before BC index date, evidence of BRCA mutation (BRCA+), evidence of metastasis, and no previous cancers were included. Analyses were stratified by the overall BRCA+ cohort and 4 molecular phenotypes: HER2+/HR- (human epidermal growth factor 2/hormone receptor), HER2−/HR+, HER2+/HR+, and triple negative BC (TNBC; HER2−/HR-). Seizures were identified using diagnosis codes and natural language processing. Incidence, occurrence rates, and cumulative incidence of seizures from the diagnosis of metastasis to the end of follow up were calculated. Comparisons were made between phenotypes and stratified on PARP inhibitor use, diagnosed brain metastases, history of seizures, and anticonvulsants use before BC. All comparisons included age at metastasis, number of prior lines of treatment, and metastasis location as covariates.

Results

27.8% of 7941 BRCA+ patients had ≥1 seizure over a mean follow-up time of 2.35 years. Incidence and occurrence rates were 11.83 (95% CI: 11.35–12.33) and 201.3 (95% CI: 198.05–204.50), respectively, per 100 person-years. HER2−/HR+ and TNBC patients had the lowest and highest seizure incidence rates, respectively (10.94 [95% CI: 10.23–11.71] and 16.83 [95% CI: 15.34–18.46]). With HER2−/HR+ as the reference group in a competing risk analysis, TNBC (hazard ratio, HR = 1.35; 95%CI: 1.21, 1.52; p < 0.001) and HER2+/HR- (HR = 1.29; 95%CI: 1.07, 1.56; p < 0.01) patients had a greater risk of seizures. Patients with diagnosed brain metastases or a history of seizures had higher seizure rates. Incidence trended higher with PARP inhibitor use, but patient numbers were low.

Conclusions

This study provides novel real-world evidence on seizure incidence rates in BRCA+ BC patients, even those without diagnosed brain metastases, and underscores the need to understand patients’ tumor phenotypes when assessing seizure risk. These findings may have implications for clinical practice and assessment of benefit-risk ratios of new therapeutic agents.
Mortality and disability-adjusted life years for smoking-attributed cancers from 1990 to 2019 in the north Africa and middle east countries: a systematic analysis for the global burden of disease study 2019
Authors: Rezakhani Leila , Darbandi Mitra , Khorrami Zahra , Rahmati Shima , Shadmani Fatemeh Khosravi
Published: January 2023

Aim and background

Smoking is a modifiable risk factor for cancers. The aim of the study is to estimate the trend of mortality and DALYs of smoking-attributed cancers in the North Africa and Middle East (NAME) countries.

Methods

In this study, estimates from the Global Burden of Disease 2019 (GBD-2019) study were used to report the mortality and DALYs for 16 smoking-attributed cancers. The mortality and DALYs rates from smoking-attributed cancers were evaluated by age, sex, and the 21 countries of the NAME countries from 1990 to 2019.

Results

Age standardized mortality rates (ASMR) for the 29 smoking-attributed cancers in the NAME countries in 1990 and 2019 were estimated to be 24.7 (95% Uncertainty Interval: 21.5, 27.8) and 22.4 (95%UI: 19.8, 25.4) respectively, which shows a 9.2% decrease in the three decades. DALYs/100,000 for smoking-attributed cancers was, also, estimated to be 600.3 (95%UI: 521.6, 682.6) and 515.6 (95%UI: 454.9, 585.4) respectively, which indicates a 14.1% decreased in these three decades. In the last three decades, the percentage changes in DALYs/100,000 for smoking-attributed cancers in males and females were − 0.16 and − 0.03, respectively. Plus, The percentage changes in ASMR in males and females were − 12% and 8%, respectively. Furthermore, The highest ASMR and DALYs were observed in Lebanon, Turkey, and Palestine in 2019.

Conclusion

The mortality rates of cancers from smoking have increased substantially among females, in most countries of the NAME region, in recent years. The burden caused by smoking can be reduced through modifying lifestyle and applying strict laws on smoking by governments and policymakers.
The impact of antipsychotic adherence on acute care utilization
Authors: Perkins Anthony J. , Khandker Rezaul , Overley Ashley , Solid Craig A. , Chekani Farid , Roberts Anna , Dexter Paul , Boustani Malaz A. , Hulvershorn Leslie
Published: January 2023

Background

Non-adherence to psychotropic medications is common in schizophrenia and bipolar disorders (BDs) leading to adverse outcomes. We examined patterns of antipsychotic use in schizophrenia and BD and their impact on subsequent acute care utilization.

Methods

We used electronic health record (EHR) data of 577 individuals with schizophrenia, 795 with BD, and 618 using antipsychotics without a diagnosis of either illness at two large health systems. We structured three antipsychotics exposure variables: the proportion of days covered (PDC) to measure adherence; medication switch as a new antipsychotic prescription that was different than the initial antipsychotic; and medication stoppage as the lack of an antipsychotic order or fill data in the EHR after the date when the previous supply would have been depleted. Outcome measures included the frequency of inpatient and emergency department (ED) visits up to 12 months after treatment initiation.

Results

Approximately half of the study population were adherent to their antipsychotic medication (a PDC ≥ 0.80): 53.6% of those with schizophrenia, 52.4% of those with BD, and 50.3% of those without either diagnosis. Among schizophrenia patients, 22.5% switched medications and 15.1% stopped therapy. Switching and stopping occurred in 15.8% and 15.1% of BD patients and 7.4% and 20.1% of those without either diagnosis, respectively. Across the three cohorts, non-adherence, switching, and stopping therapy were all associated with increased acute care utilization, even after adjusting for baseline demographics, health insurance, past acute care utilization, and comorbidity.

Conclusion

Non-continuous antipsychotic use is common and associated with high acute care utilization.
Evaluating HIV Rapid/Point of Care Testing among Risk Factor Groups in Ontario, 2011 to 2018
Authors: Rilkoff Heather , Hussain Hadia , Liu Juan , English Ken , Lush Joanne , Sullivan Ashleigh , Tran Vanessa , Allen Vanessa , Murti Michelle
Published: January 2023

Objectives

In 2014, Ontario’s Point-of-Care (POC) test providers were advised to focus efforts on provincially defined priority populations who experience a greater risk of HIV. Our objective was to describe the POC program before, during and after this change, including tester characteristics, follow-up testing results, positive predictive value (PPV) over time, and trends and characteristics of those with reactive test results without a confirmatory serological specimen.

Methods

Test-level data of POC screening and confirmatory results were extracted from the Public Health Ontario HIV Datamart. Final test results were defined based on results of the confirmatory blood sample, or the POC test for “non-reactive” tests. Testing volumes, percent of total tests, percent positivity and PPV were calculated overall, annually, and by exposure group.

Results

Overall testing volumes decreased by 39.8% between 2014 and 2018. The majority of confirmed positive tests were in the men who have sex with men (MSM) exposure category, followed by HIV-endemic and heterosexual – no identified risk (heterosexual—NIR). Overall percent positivity decreased from 0.59% in 2011 to 0.42% in 2015 (change of 0.17%, 95% CI 0.03% to 0.31%), increasing to 0.69% in 2018 (change of 0.27%, 95% CI 0.20% to 0.34%). Increases in percent positivity corresponded with a decrease in the overall proportion of tests conducted in low-risk populations. When compared to the heterosexual-NIR category, PPV was significantly higher for men who have sex with men – people who use injection drugs (MSM-PWID) (52.7% compared to 100%, P < .001), MSM (52.7% compared to 95.4%, P < .001), HIV-endemic (52.7% compared to 91.5%, P < .001), heterosexual – partner with identified risk (heterosexual—PIR) (52.7% compared to 77.3%, P = .042), and people who use injection drugs (PWID) (52.7% compared to 81.3%, P = 0.007). A total of 13.5% of reactive POC results did not have a serological sample submitted.

Conclusions

Targeted testing towards populations at higher risk of HIV improved the overall test performance characteristics of Ontario’s POC testing program. While not unexpected, the large discrepancies between PPV in higher-risk, compared to lower-risk populations, suggests the need for greater awareness and messaging of the likelihood of false positive test results in different populations.
Plant and animal protein intake and its association with depression, anxiety, and stress among Iranian women
Authors: Sheikhi Ali , Siassi Fereydoun , Djazayery Abolghassem , Guilani Bijan , Azadbakht Leila
Published: January 2023

Background

Mental disorders are conditions that affect the usual function of the brain, causing a huge burden on societies. The causes are often unclear, but previous research has pointed out, as is the case with many other diseases, that nutrition could have a major role in it. Amino acids, the building blocks of proteins, are the main precursor of neurotransmitters (the chemical messengers in the brain) malfunction of which is heavily associated with a wide range of brain disorders.

Methods

We assumed different sources of dietary protein could have different impacts on mental well-being. Hence, we decided to collect the nutritional data (with a validated and reliable semi-quantitative food-frequency questionnaire) from a sample of 489 Iranian women and investigate the association between animal and plant protein sources and the risk of depression, anxiety, and stress. Symptoms of these mental disorders were assessed using a validated Depression, Anxiety, and Stress Scales (DASS) questionnaire with 21 items.

Results

After multivariable adjustment, it was shown that women in the highest tertile of animal protein intake were more likely to show symptoms of depression (OR: 2.63; 95% CI: 1.45, 4.71; P = 0.001), anxiety (OR: 1.83; 95% CI: 1.04, 3.22; P = 0.03), and stress (OR: 3.66; 95% CI: 2.06, 6.50; p < 0.001). While no significant association was seen between plant protein and any of the studied mental disorders.

Conclusion

Overall, our findings suggest that a diet high in animal protein could predispose individuals to mental illnesses.
Proposal of a diagnostic algorithm for myofascial trigger points based on a multiple correspondence analysis of cross-sectional data
Authors: Baeumler Petra , Hupe Kerstin , Irnich Dominik
Published: January 2023

Background

Myofascial trigger points (MTrPS), the morphological correlate of myfascial pain syndromes (MPS), contribute to the worldwide high chronic pain burden. However, uncertainty about MTrP diagnostic criteria remains. Aim of this cross-sectional study was to characterize clusters of diagnostic criteria assessable during physical examination that might guide MTrP diagnosis.

Methods

Thirteen MTrP diagnostic criteria proposed in relevant literature were assessed by standardized examinations in the trapezius and levator scapulae muscles of 61 chronic pain patients undergoing an interdisciplinary pain assessment. Hierarchical cluster analysis from multiple correspondence analysis was applied to data of the four muscles separately. Examining physicians classified the findings as MTrP, sufficient for diagnosis of an MPS and/or relevant for the patients’ pain condition.

Results

Taut bands, hypersensitive spots within a taut band, nodules within a taut band and referred pain (classical diagnostic criteria) were most frequent (28–66% M. trapezius, 8–21% M. levator scapulae). Restricted range of motion, pain during contraction, pain exacerbation during emotional stress, muscular weakness, jump sign, local twitch response and autonomic phenomena (complementary diagnostic criteria) occurred in 2–25% and hypersensitive spots and nodules outside of a taut band in 2–7% of the cases. Four clusters emerged: (1) no or just one diagnostic criterion, mostly a taut band alone; (2) a hypersensitive spot and/or nodule outside of a taut band partly in combination with complementary diagnostic criteria; (3) at least two classical diagnostic criteria (mostly a taut band containing a hypersensitive spot) partly in combination with complementary diagnostic criteria; (4) at least two, rather three, classical diagnostic criteria always in combination with complementary diagnostic criteria. Referred pain was specific to cluster 3 and 4. Among classical diagnostic criteria, palpable nodules within a taut band contributed least, and among complementary diagnostic criteria, restricted range of motion and pain during contraction contributed most to data representation.

Conclusion

We propose that the definite diagnosis of an MTrP requires a hypersensitive spot potentially felt as a nodule located within a taut band in addition to either referred pain, a local twitch response or at least two complementary diagnostic criteria, whereby signs of muscular dysfunction take on greater importance.
“I never should have been a doctor”: a qualitative study of imposter phenomenon among internal medicine residents
Authors: Chodoff Alaina , Conyers Lynae , Wright Scott , Levine Rachel
Published: January 2023

Introduction

Imposter phenomenon is common among medical trainees and may influence learning and professional development. The authors sought to describe imposter phenomenon among internal medicine residents.

Methods

In 2020, using emailed invites we recruited a convenience sample of 28 internal medicine residents from a teaching hospital in Baltimore, Maryland to participate in an exploratory qualitative study. In one-on-one interviews, informants described experiences of imposter phenomenon during residency training. Using thematic analysis to identify meaningful segments of text, the authors developed a coding framework and iteratively identified and refined themes. Informants completed the Clance Imposter Phenomenon Scale.

Results

Informants described feelings and thoughts related to imposter phenomenon, the contexts in which they developed and the impact on learning. Imposter phenomenon has profound effects on residents including: powerful and persistent feelings of inadequacy and habitual comparisons with others. Distinct contexts shaping imposter phenomenon included: changing roles with increasing responsibilities; constant scrutiny; and rigid medical hierarchy. Learning was impacted by inappropriate expectations, difficulty processing feedback, and mental energy diverted to impression management.

Discussion

Internal medicine residents routinely experience imposter phenomenon; these feelings distort residents’ sense of self confidence and competence and may impact learning. Modifiable aspects of the clinical learning environment exacerbate imposter phenomenon and thus can be acted upon to mitigate imposter phenomenon and promote learning among medical trainees.
Differences in international medical graduates’ letters of recommendation by gender in pulmonary and critical care medicine: a cohort analysis
Authors: Byrd Kaitland M. , Jain Snigdha , Choudhuri Irada , Çoruh Başak , McSparron Jakob I. , Viglianti Elizabeth M.
Published: January 2023

Background

International Medical Graduates (IMGs) encounter barriers as they seek to match into fellowship programs in the United States (US). This study’s objective is to determine if there are differences in letters of recommendation written for IMGs compared to U.S. Medical Graduates (USMGs) applying to pulmonary and critical care medicine (PCCM) fellowship programs.

Methods

All applications submitted to a PCCM fellowship program in 2021 were included in this study. The applicant demographics and accomplishments were mined from applications. The gender of letter writers was identified by the author’s pronouns on professional websites. Word count and language differences in the letters were analyzed for each applicant using the Linguistic Inquiry and Word Count (LWIC2015) program. Multivariable linear regressions were performed controlling for applicant characteristics to identify if IMG status was associated with total word count and degree of support, measured by a composite outcome encompassing several categories of adjectives, compared to USMG status.

Results

Of the 573 applications, most of the applicants were USMGs (72%, N = 334/573). When adjusting for applicant characteristics, IMG applicants had shorter letters of recommendation (87.81 total words shorter 95% CI: − 118.61, − 57.00, p-value < 0.01) and less supportive letters (4.79 composite words shorter 95% CI: − 6.61, − 2.97, p-value < 0.01), as compared to USMG applicants. Notably, female IMG applicants had the biggest difference in their word counts compared to USMG applicants when the letter writer was a man.

Conclusions

IMG applicants to a PCCM fellowship received shorter and less supportive letters of recommendation compared to USMG applicants.
Describing the evidence-base for research engagement by health care providers and health care organisations: a scoping review
Authors: Yoong Sze Lin , Bolsewicz Katarzyna , Reilly Kathryn , Williams Christopher , Wolfenden Luke , Grady Alice , Kingsland Melanie , Finch Meghan , Wiggers John
Published: January 2023

Background

Having a research-engaged health and medical workforce is associated with improvements in clinical outcomes for patients. As such, there has been significant government investment internationally to support health care organisations and services to increase staff engagement with research.

Objectives

This scoping review sought to provide an overview of the literature describing strategies employed to increase research engagement by health care providers and organisations, and to undertake a qualitative analysis to generate a list of research engagement strategies.

Methods

A scoping review using systematic search strategies was undertaken to locate peer-review publications and grey literature related to research engagement by health care providers and organisations. Research engagement was defined as a ‘deliberate set of intellectual and practical activities undertaken by health care staff and organisations to conduct research’. A database search of electronic records was performed with no limit on publication date. Publications were included regardless of study type (excluding systematic reviews) and categorised as either databased (presenting data or new analysis of existing data) and non-databased (no new data or analyses). Databased publications were further classified according to study type, study design and setting. A qualitative synthesis using a Framework Approach was undertaken with all studies that described a strategy to improve research engagement.

Results

A total of 152 publications were included in this study with 54% categorised as non-databased. Of the databased articles, the majority (72%) were descriptive studies describing prevalence of correlates of research engagement, 17 (25%) described intervention studies where only two were controlled studies. The following research engagement strategies were identified: i) dual skilled team/staff, ii) resources or physical infrastructure, iii) incentives, iv) leadership support of research, v) education/training, vi) networks, vii) forming partnerships or collaborations and viii) overall leadership structure of entity.

Conclusions

The literature on research engagement is primarily opinion-based and descriptive in nature. To provide the evidence needed to inform strategies, this needs to progress beyond descriptive to more rigorous well-designed intervention research.