bluuebunny/crossref_metadata_2025 huggingface dataset:
Femtosecond laser–assisted intraocular lens exchange
Authors: Fram Nicole R. , Masket Samuel , Alsetri Hasan , Pham Don
Published: July 2021

Intraocular lens (IOL) exchange in patients with anterior capsule contraction resulting from phimosis can complicate IOL exchange as the fibrotic anterior capsule must be cut to gain access to the IOL. Maintaining curvilinear capsulotomy is particularly important when the desired outcome is bag-to-bag IOL exchange. Similarly, when the posterior capsule is open, properly sized curvilinear anterior capsulotomy will allow for optic capture and further stability of the exchanged IOL. Secondary capsulotomy size ranged from 4.9 to 5.0 mm, and the energy was set at 4 to 10 μJ depending on diffusiveness of the anterior capsule. The femtosecond laser was adapted to create a secondary anterior capsulotomy to facilitate IOL exchange.
Management of Kasabach–Merritt Phenomenon With Transarterial Embolization in Patients With Kaposiform Hemangioendothelioma
Authors: Celis-Jiménez Alejandro , Meza-López Ana Sofía , Santana-Cárdenas Carmen Leticia , Cortés-Barrios Delma Gabriela , Requena-Torres Bertha Graciela , Tiznado-García Héctor Manuel
Published: July 2021

Objectives:

The aim of this study is to demonstrate, through a series of four cases, that endovascular approach through transarterial embolization is a useful adjunctive tool and rapid method to reduce tumoral blood flow supply in patients with Kaposiform hemangioendothelioma (KHE) who present with Kasabach–Merritt phenomenon (KMP).

Methods:

We reviewed clinical records of four patients from January 2019 to December 2019 in Unidad Médica de Alta Especialidad Hospital de Pediatría in Centro Médico Nacional de Occidente with clinical diagnosis of KHE who presented with KMP. Patients were treated with transarterial embolization and followed from the time of diagnosis through 6 months following endovascular procedure.

Results:

Serum hemoglobin and platelet counts improved within 48 hours following embolization and were sustained for at least 6 months. Tumors notably decreased in size and improved in color in 3 of 4 patients.

Conclusions:

Transarterial embolization in this group of patients showed a rapid increase in the platelet count, which can be traduced as a good adjunctive treatment for patients that have a slow improvement in platelet count receiving standard medical treatment alone.
Selective Unique Signs of Meniscus Tears as Visualized by Magnetic Resonance Imaging
Authors: Esdaille Caldon Jayson , Marrero Daniel , Laurencin Cato T.
Published: July 2021

The meniscus is an organized collection of fibrocartilaginous tissue that is located between the femoral condyles and the tibial plateau of the knee which primarily assists with load transmission. The complex composition of articulating soft-tissue structures in the knee causes the menisci to become a common source of injury, especially in the realm of athletic trauma. Magnetic resonance imaging (MRI) has become the imaging modality of choice for evaluating patients with suspected meniscal pathology because of its numerous advantages over plain radiographs. Most forms of meniscal tears have classic MRI findings and are used in correlation with physical examination findings to confirm or rule out a diagnosis. These imaging findings are referred to as signs and have been well studied, and the associated eponyms for each sign are well published throughout the literature. This article will review and describe a unique selection of meniscal pathology as visualized by MRI that is more commonly published in musculoskeletal radiology literature when compared with orthopedics and sports medicine literature.
Lifetime Cost and Quality-Adjusted Life-Years Across Management Options for Small- and Medium-Sized Sporadic Vestibular Schwannoma
Authors: Macielak Robert J. , Thao Viengneesee , Borah Bijan J. , Moriarty James P. , Marinelli John P. , Van Gompel Jamie J. , Carlson Matthew L.
Published: July 2021

Objective:

Despite the growing emphasis on healthcare costs, limited data address this aspect of care within the vestibular schwannoma (VS) literature. We sought to determine which strategy confers the lowest lifetime cost and greatest quality-adjusted life-years (QALYs) for patients with small- to medium-sized sporadic VS tumors.

Study Design:

A Markov model was created to determine the most cost-effective management algorithm. Tumor characteristics, magnetic resonance imaging surveillance schedule, treatment outcomes, and health-related quality of life values were derived from previously published data. Cost estimates were based on CMS Fee Schedule reimbursement rates.

Setting:

Economic Evaluation Service within the Kern Center for the Science of Healthcare Delivery.

Patients:

Patients diagnosed with small- to medium-sized sporadic VS.

Interventions:

Upfront microsurgery following diagnosis, upfront radiosurgery following diagnosis, observation with microsurgery reserved for observed tumor growth, and observation with radiosurgery reserved for observed tumor growth.

Results:

Across patient ages at time of diagnosis ranging from 18 to 70 years, observation with subsequent radiosurgery used for tumor growth was the most cost-effective management algorithm while upfront microsurgery was the least. When presented with a hypothetical 50-year-old patient, the strategy with the lowest lifetime cost and highest QALYs was observation with subsequent radiosurgery reserved for tumor growth ($32,161, 14.11 QALY), followed by observation with microsurgery reserved for tumor growth ($34,503, 13.94 QALY), upfront radiosurgery ($43,456, 14.02 QALY), and lastly, upfront microsurgery ($47,252, 13.60 QALY). Sensitivity analyses varying mortality rates, estimated costs, health-related quality of life, and progression to nonserviceable hearing demonstrated consistent ranking among treatments.

Conclusions:

When considering initial management of small- and medium-sized sporadic VSs, neither lifetime cost nor QALYs support upfront microsurgery or radiosurgery, even for younger patients. Initial observation with serial imaging, reserving radiosurgery or microsurgery for patients exhibiting tumor growth, confers the greatest potential for optimized lifetime healthcare cost and QALY outcomes.
Real-life utility and diagnostic accuracy of a home-performed fecal calprotectin test to predict endoscopic activity in patients with inflammatory bowel disease under maintenance treatment with adalimumab
Authors: Orfanoudaki Eleni , Drygiannakis Ioannis , Theodoraki Eirini , Foteinogiannopoulou Kalliopi , Mantaka Aikaterini , Koutroubakis Ioannis E.
Published: July 2021

Aims

The home-performed fecal calprotectin (FC) test has been proposed for the remote management of inflammatory bowel disease (IBD) patients. We present our real-world experience on the use of FC home testing in IBD patients under maintenance treatment with adalimumab.

Methods

Consecutive IBD patients on maintenance treatment with adalimumab were studied retrospectively on the basis of prospectively recorded data. FC calprotectin home test (IBDoc, Βühlmann Laboratories AG, Schönenbuch, Switzerland) was analyzed alongside sufficient information on baseline characteristics, follow-up data and treatment modifications, as well as serum biomarkers and endoscopic assessment data on the basis of validated endoscopic scores.

Results

From a total of 72 IBD patients under maintenance treatment with adalimumab, 65 (90%) showed compliance with performing the home FC test. FC values were significantly higher in patients who finally needed treatment modification (37%) compared with those who were maintained on stable treatment (63%) (761 μg/g [537–1000] vs. 108 [41–335], P < 0.0001). In the logistic regression analysis FC and erythrocyte sedimentation rate (ESR) were independently correlated with endoscopically active disease (odds ratio: 1.003; 95% confidence interval, 1.001–1.006, P < 0.01 and odds ratio: 1.058; 95% confidence interval, 1.013–1.105, P < 0.05). FC identified patients with endoscopically active disease more effectively than other biomarkers with an area under the receiver operating characteristic curve of 0.78. FC levels >413 μg/g had a sensitivity of 75% and a specificity of 76% in predicting active disease in endoscopy.

Conclusions

These first real-life results indicate that in IBD patients under maintenance treatment with adalimumab FC home test is a valuable tool with high compliance rates that performs better than the other biomarkers in predicting disease endoscopic activity.
Efficacy and safety of endoscopic resection techniques of large colorectal lesions: experience of a referral center in Italy
Authors: Papparella Luigi Giovanni , Barbaro Federico , Pecere Silvia , Gibiino Giulia , Burrelli Scotti Giorgia , Napoli Marco , Boskoski Ivo , Petruzziello Lucio , Costamagna Guido
Published: July 2021

Background

Endoscopic mucosal resection and submucosal dissection (ESD) are treatments of choice for superficial neoplastic colorectal lesions. Only a few studies have compared these techniques.

Aim

To compare the efficacy and safety of endoscopic piecemeal mucosal resection (EPMR), ESD and hybrid-endoscopic submucosal dissection (H-ESD) of large colorectal lesions in a Western endoscopic center.

Methods

This is a retrospective analysis on a prospective medical database of consecutive colorectal superficial lesions larger than 20 mm, resected by EPMR, ESD or H-ESD collected from 2015 to 2019.

Results

Two hundred twenty-nine colorectal lesions were included. All lesions were completely endoscopically resected, 65.9% by EPMR, 19.7% by ESD and 14.4% by H-ESD. Endoscopic control after the index procedure was available for 86.5% patients. Among these patients, 80% had a second follow-up colonoscopy. The overall recurrence rate was 13.2, 0 and 6.1% for EPMR, ESD and H-ESD respectively, with a significant difference between EPMR and ESD. All recurrences were endoscopically treated during follow-up procedures. Risk of complications was not significantly different between the three groups.

Conclusions

EPMR, ESD and H-ESD are effective and safe procedures. Recurrence rate in EPMR was higher but can be managed endoscopically with high success rates. EPMR is faster and technically simpler so should be considered a potential first-line therapy for colorectal superficial neoplastic lesions.
An overview of nuclear medicine research in the UK and the landscape for clinical adoption
Authors: Young Jennifer D. , Jauregui-Osoro Maite , Wong Wai-Lup , Cooper Margaret S. , Cook Gary , Barrington Sally F. , Ma Michelle T. , Blower Philip J. , Aboagye Eric O.
Published: July 2021

Background and objectives

Nuclear medicine contributes greatly to the clinical management of patients and experimental medicine. This report aims to (1) outline the current landscape of nuclear medicine research in the UK, including current facilities and recent or ongoing clinical studies and (2) provide information about the available pathways for clinical adoption and NHS funding (commissioning) of radiopharmaceuticals.

Methods

Evidence was obtained through database searches for UK-based nuclear medicine clinical studies and by conducting a questionnaire-based survey of UK radiopharmaceutical production facilities. A recent history of clinical commissioning, either through recommendations from the National Institute for Health and Care Excellence (NICE) or through NHS specialised services commissioning, was compiled from publicly available documents and policies.

Results

The collected data highlighted the UK’s active nuclear medicine research community and recent investment in new facilities and upgrades. All commissioning routes favour radiopharmaceuticals that have marketing authorisation and since 2017 there has been a requirement to demonstrate both clinical and cost-effectiveness. Whilst radiopharmaceuticals for molecular radiotherapy are well suited to these commissioning pathways, diagnostic radiotracers have not historically been assessed in this manner.

Conclusions

We hope that by collating this information we will provide stimulus for future discussion and consensus statements around this topic.
Correlation of 4′-[methyl-11C]-thiothymidine PET with Ki-67 immunohistochemistry separately in patients with newly diagnosed and recurrent gliomas
Authors: Norikane Takashi , Mitamura Katsuya , Yamamoto Yuka , Hatakeyama Tetsuhiro , Miyake Keisuke , Toyohara Jun , Nishiyama Yoshihiro
Published: July 2021

Objective

4′-[methyl-11C]-thiothymidine (4DST) uptake on PET was correlated with proliferative activity separately in patients with newly diagnosed and recurrent gliomas.

Methods

A total of 29 patients, 18 with newly diagnosed gliomas and 11 with recurrent gliomas who underwent 4DST PET/computed tomography (CT) were available for a retrospective analysis of prospectively collected data. The maximum standardized uptake value (SUVmax) of tumor (T) and the mean SUV of normal contralateral hemisphere (N) were calculated, and the tumor-to-normal (T/N) ratio was determined. Proliferative tumor volume (PTV) and total lesion proliferation (TLP) were also calculated. Proliferative activity as indicated by the Ki-67 index was estimated in tissue specimens. Immunohistochemical findings were correlated with 4DST PET parameters.

Results

All gliomas but three newly diagnosed gliomas had 4DST uptake on PET. No significant differences in SUVmax, T/N ratio, PTV, or TLP were observed between the newly diagnosed and recurrent gliomas. In the former, correlations between SUVmax (r = 0.57, P = 0.02), T/N ratio (r = 0.51, P = 0.03), PTV (r = 0.74, P < 0.001), and TLP (r = 0.76, P < 0.001) and the Ki-67 index were found. In the latter, the results did not seem to suggest any correlations between any of the PET parameters and Ki-67 index.

Conclusion

Although preliminary, these results suggest that 4DST PET may be useful for the noninvasive evaluation of proliferation in patients with newly diagnosed gliomas. These data in a small recurrent patient population do not support a clear-cut correlation between 4DST uptake and proliferation.
Involvement of Jordanian Patients and Their Families in Decision Making Near End of Life, Challenges and Recommendations
Authors: Othman Elham H. , Khalaf Inaam Abdallah , Zeilani Ruqayya , Nabolsi Manar , Majali Sawsan , Abdalrahim Maysoon , Shamieh Omar
Published: July 2021

This study aims to explore the challenges in involving patients and their families in decision making near end of life and to provide recommendations to overcome these challenges. A qualitative descriptive phenomenological approach was used with a purposive sample of 8 patients, 7 family caregivers, 7 nurses, and 6 physicians from 2 institutions that provide palliative and end-of-life care services in Jordan. Data were collected using interviews with patients and family caregivers and focus group discussions with nurses and physicians. Colaizzi's method was used to analyze the data.

The thematic analysis revealed 5 themes representing the participants' experiences of challenges with decision making near end of life. The identified challenges are (1) struggle with lack of information; (2) improper communication; (3) patient's or family's decision: the cultural taboo; (4) health care providers prefer staying in their comfort zone; and (5) the paradox of surviving and letting go. In addition, the participants endorsed several recommendations to raise public awareness of palliative and end-of-life care, amplify the patients' voice, and raise the bar of communication sensitivity.

Decision making near the end of life is a challenge. However, the current study highlighted several areas for improvement that can improve the process and optimize patients' and their families' involvement.
“We Want to Sign It, But We Can't Do It”
Authors: Lee Hsin-Tzu Sophie , Yang Chia-Ling , Chen Ting-Ru , Leu Sei-Ven , Hu Wen-Yu
Published: July 2021

This study aimed to clarify the experiences of family members of older adult residents regarding the signing of an advance directive in the context of a Chinese culture. Twenty family members of older residents in a long-term care facility participated in face-to-face interviews, and the researchers conducted a thematic analysis of observation field notes and interview transcripts. A content analysis of the interviews revealed 4 themes concerning the refusal to sign advance directives: resident decision, group decision, not entitled to decide, and random decision. Health providers may serve as mediators and pass on the residents' views regarding their end-of-life care to their families after holding discussions with residents and their families separately to ensure that an agreeable decision regarding the modes and objectives of EOL care is reached and that such a decision respects the right of the patient to choose.
The Role of External Genital Lesions in Human Immunodeficiency Virus Seroconversion Among Men Participating in a Multinational Study
Authors: Sudenga Staci L. , Lotspeich Sarah C. , Nyitray Alan G. , Sirak Bradley , Shepherd Bryan E. , Messina Jane , Sereday Karen A. , Silva Roberto Carvalho , Abrahamsen Martha , Baggio Maria Luiza , Quiterio Manuel , Lazcano-Ponce Eduardo , Villa Luisa , Giuliano Anna R.
Published: July 2021

Background

Studies in women have shown an increased risk of human immunodeficiency virus (HIV) acquisition with prior human papilloma virus (HPV) infection; however, few studies have been conducted among men. Our objective was to assess whether HPV-related external genital lesions (EGLs) increase risk of HIV seroconversion among men.

Methods

A total of 1379 HIV-negative men aged 18 to 70 years from the United States, Mexico, and Brazil were followed for up to 7 years and underwent clinical examination for EGLs and blood draws every 6 months. Human immunodeficiency virus seroconversion was assessed in archived serum. Cox proportional hazards and marginal structural models assessed the association between EGL status and time to HIV seroconversion.

Results

Twenty-nine participants HIV seroconverted during follow-up. Older age was associated with a lower hazard of HIV seroconversion. We found no significant difference in the risk of HIV seroconversion between men with and without EGLs (adjusted hazard ratio, 0.94; 95% confidence interval, 0.32–2.74). Stratified analyses focusing on men that have sex with men found no association between EGLs and HIV seroconversion risk (hazards ratio, 0.63; 95% confidence interval, 0.00–1.86).

Conclusions

External genital lesions were not associated with higher risk for HIV seroconversion in this multinational population, although statistical power was limited as there were few HIV seroconversions. Results may differ in populations at higher risk for HIV.
DFSP of the Breast: Histomorphological, Immunohistochemical, and Molecular Features of a Rare Case in an Unusual Location
Authors: Laharwani Hansini , Prakash Varsha , Walley Debbie , Akhtar Israh
Published: July 2021

We present a case of a 21-year-old female with a vague nontender mass in the lower inner quadrant of the left breast discovered incidentally on chest imaging following trauma. A breast ultrasound demonstrated an 8×6×8 mm irregular hyperechoic mass at the 7 o’clock position of the left breast, 9 cm from the nipple. The mass was graded Breast Imaging Reporting and Data System (BI-RADS) category 4 (suspicious finding). An ultrasound-guided biopsy of the mass showed a proliferation of monotonous spindled cells in a storiform pattern with tapered nuclei with infiltration into the adipose tissue. No normal breast elements were identified in the biopsy. Myofibroblastoma was the first differential diagnosis; however, the characteristic infiltrative pattern of the tumor mandated additional tests including fluorescence in situ hybridization to rule out a dermatofibrosarcoma protruberance (DFSP). Immunohistochemical staining showed positive staining for CD34, which can be positive in myofibroblastoma also. However, fluorescence in situ hybridization demonstrated a platelet-derived growth factor B (22q13.1) gene rearrangement confirming a diagnosis of DFSP. The patient underwent a wide local excision of the DFSP for definitive treatment. She is doing well with no recurrence reported so far, after 15 months of follow-up. Conventional DFSP does not metastasize but is prone to recurrence making wide margins imperative for definitive treatment.
Pheochromocytoma
Authors: Liu Zhonghua , Ma Junsheng , Jimenez Camilo , Zhang Miao
Published: July 2021

Pheochromocytomas are rare neuroendocrine tumors arising from chromaffin cells in the adrenal medulla. They may occur sporadically or in the context of hereditary syndromes. All pheochromocytomas are considered to have malignant potential (defined as risk of metastasis, not local invasion). The use of grading systems with incorporated clinical and histopathologic parameters can help but not definitively predict the metastatic potential of pheochromocytomas. The recent discovery of susceptibility genes provided new insights into the pathogenesis and introduced additional approaches to estimate the metastatic risk of pheochromocytoma. However, the prevalence of these genetic signatures in pheochromocytomas has yet to be fully addressed. Therefore, in the present study, we retrospectively reviewed cases of pheochromocytoma from 1980 to 2018 in the archives of our institution. Three hundred ninety cases were identified, and their clinicopathologic characteristics and genetic statuses were analyzed. About 25% of the cases had metastases, which were more common in older patients (median, 49 y) than in younger ones. Univariate and multivariate analyses revealed that older age, Hispanic ethnicity, metastasis, and large primary tumor size were markedly associated with poor overall survival. In contrast, family history of pheochromocytoma, lack of symptoms, and bilateral adrenal involvement were associated with better survival. About 37% of the pheochromocytomas were associated with inherited syndromes. About 52% of tested patients had pathogenic mutations of pheochromocytoma susceptibility genes. Of these, succinate dehydrogenase B gene mutation had the strongest association with metastasis. These data support that genetic testing should be offered to all patients with pheochromocytoma.
Seasonal Trends in Pediatric Respiratory Illnesses
Authors: Tse Gabriel , McLean Lianne
Published: July 2021

Objectives

Google Trends is an emerging tool that allows users to analyze search queries, showing when certain topics are searched most often. Multiple studies have compared Google Trends to epidemiological data of health conditions, but pediatric specific illnesses have not yet been investigated. An association between disease incidence and Google Trends data may help facilitate precision outreach in the form of digital resources and promotion. We sought to examine the relationship between Google Trends data and measured incidence of bronchiolitis and croup.

Methods

We carried out a Google Trends search using the terms “bronchiolitis” and “croup” on July 24, 2019. The number of positive respiratory syncytial virus and parainfluenza tests published by the Public Health Agency of Canada was used to estimate incidence of bronchiolitis and croup, respectively. Emergency department discharge data were used to measure the number of patients with bronchiolitis and croup presenting to a Canadian pediatric hospital. Data from January 1, 2015, to December 31, 2018, were used for analysis.

Results

Google Trends revealed clear seasonal variation in search volume for both bronchiolitis and croup in keeping with known epidemiological data for these conditions. For data on bronchiolitis, Google Trends correlated strongly with Canadian Public Health and our hospital data. A positive correlation was also found with croup.

Conclusions

Google Trends correlates with both laboratory-based and hospital incidence of respiratory viral diagnoses. This novel data source has implications for tracking disease epidemiology, tailoring health information, and providing precision outreach tools to patients and their families.
Pediatric Unintentional Fall-Related Injuries in a Statewide Trauma Registry
Authors: Davis Jonathan , Young Tracy , Casteel Carri , Peek-Asa Corinne , Torner James
Published: July 2021

Objectives

The purpose of the study was to evaluate patterns of fall-related injury through childhood and identify risk factors for more severe fall-related injuries with the goal of informing targeted prevention strategies for different ages.

Methods

The study population consisted of pediatric patients in the Iowa Trauma Registry from January 1, 2010, to December 31, 2014, who sustained an unintentional fall-related injury (N = 3856 patients). Multinomial logistic regression analysis was used to predict injury severity. Adjusted odds ratios were calculated characterizing the relationship between fall severity and age, sex, race, and fall type.

Results

More males (62%) sustained a fall-related injury during the study period when compared with females (38%; P < 0.0001). Head injuries were the most common type of injury in the younger than 1 year age group (77%), whereas fractures were the predominant injury type in all other age groups, followed by head injuries. Those younger than 1 year (adjusted odds ratio, 4.0; 95% confidence interval, 2.36–6.90) and aged 15 to 18 years (adjusted odds ratio, 1.9; 95% confidence interval, 1.17–3.03) were more likely to have an Injury Severity Score of ≥16 than those aged 10 to 14 years.

Conclusions

Recommendations and prevention strategies need to focus on specific risk factors to reduce the harm of multilevel falls. As we have shown, patterns of fall injuries presenting to trauma hospitals differ by age, thus suggesting that prevention strategies focus on specific age groups.
Association of County-Level Availability of Pediatricians With Emergency Department Visits
Authors: Michelson Kenneth A. , Cushing Anna M. , Bucholz Emily M.
Published: July 2021

Objectives

The relationship between pediatrician availability and emergency department (ED) attendance is uncertain. We determined whether children in counties with more pediatricians had fewer ED visits.

Methods

We conducted a cross-sectional study of all ED visits among children younger than 18 years from 6 states. We obtained ED visit incidences by county and assessed the relationship to pediatrician density (pediatricians per 1000 children). Possible confounders included state, presence of an urgent care facility in the county, urban-rural status, and quartile of county-level characteristics: English-speaking, Internet access, White race, socioeconomic status, and public insurance. We estimated county-level changes in incidence by pediatrician density adjusting for state and separately for all possible confounders.

Results

Each additional pediatrician per 1000 children was associated with a 13.7% (95% confidence interval, −19.6% to −7.5%) decrease in ED visits in the state-adjusted model. In the full model, there was no association (−1.4%, 95% confidence interval, −7.2% to 4.8%). The presence of an urgent care, higher socioeconomic status score, urban status, and higher proportions of White race and nonpublic insurance were each associated with decreased ED visit rates.

Conclusions

Pediatrician density is not associated with decreased ED visits after adjusting for other county demographic factors. Increasing an area's availability of pediatricians may not affect ED attendance.
Endometrioid Tubal Intraepithelial Neoplasia and Bilateral Ovarian Microcystic Stromal Tumors Harboring APC Mutations: Report of a Case
Authors: Parra-Herran Carlos
Published: July 2021

Microcystic ovarian tumor of the ovary is a neoplasm of presumed stromal derivation characterized by CTNNB1 or APC alterations leading to nuclear β-catenin expression. This tumor has been described as unilateral and indolent in previously published series. The recently characterized endometrioid tubal intraepithelial neoplasia (eTIN) is an epithelial proliferation of the tube also characterized by nuclear β-catenin staining, and distinct from high-grade serous precursors. Herein, a case of bilateral ovarian microcystic stromal tumors and multiple left tubal eTINs discovered incidentally in a 41-yr-old woman with previous history of colon cancer is described. Both ovarian and tubal proliferations harbored APC inactivating mutations. Although history of familial adenomatous polyposis or a germline defect could not be confirmed, the history of colon cancer at a young age and the shared APC mutation in both microcystic stromal tumor and eTIN were suggestive of this possibility. Microcystic stromal tumor has been described in the setting of familial adenomatous polyposis syndrome. This case adds to this association by documenting for the first time bilateral ovarian involvement by microcystic stromal tumor. Moreover, it alerts to the possibility of endometrioid neoplasia of the fallopian tube secondary to APC mutations, a previously undescribed phenomenon.
Gucy2d selectively marks inhibitory dynorphin neurons in the spinal dorsal horn but is dispensable for pain and itch sensitivity
Authors: Serafin Elizabeth K. , Burns Robert , Yoo Judy , Baccei Mark L.
Published: July 2021

Introduction:

Inhibitory neurons in the spinal dorsal horn can be classified based on expression of neurochemical marker genes. However, these marker genes are often expressed throughout the central nervous system, which poses challenges for manipulating genetically identified spinal neurons without undesired off-target effects.

Objectives:

We investigated whether Gucy2d, previously identified as a highly selective marker of dynorphin-lineage neurons in the dorsal horn, is expressed in other locations within the adult mouse spinal cord, dorsal root ganglia (DRG), or brain. In addition, we sought to molecularly characterize Gucy2d-expressing dorsal horn neurons and investigate whether the disruption of Gucy2d gene expression affects sensitivity to itch or pain.

Methods:

In situ hybridization experiments assessed Gucy2d mRNA expression in the adult mouse spinal cord, DRG, and brain, and its colocalization with Pax2, Bhlhb5, and Pde2a in dorsal horn neurons. Knockout mice lacking Gucy2d expression were compared with littermate controls to assess sensitivity to chloroquine-induced itch and dry skin-mediated chronic itch, as well as heat, cold, or mechanical stimuli.

Results:

Gucy2d is selectively expressed in dynorphin-lineage neurons in lamina I-III of the adult mouse spinal cord but not in the brain or DRG. Spinal Gucy2d-expressing neurons are inhibitory neurons that also express the transcription factor Bhlhb5 and the cGMP-dependent phosphodiesterase Pde2a. Gucy2d knockout mice did not exhibit altered responses to itch or pain.

Conclusions:

The selective expression of Gucy2d within a subpopulation of inhibitory dorsal horn neurons may yield a means to selectively manipulate inhibitory signaling at the level of the spinal cord without effects on the brain.
Mechanism of penetrating injury mediates the risk of long-term adverse outcomes for survivors of violent trauma
Authors: Pino Elizabeth C. , Fontin Francesca , James Thea L. , Dugan Elizabeth
Published: July 2021

BACKGROUND

While hospital-based violence intervention programs are primarily designed to aid youth victims of gun violence at high risk for reinjury, the root causes and complex outcomes of community violence are varied. In this study, we examined the risk factors for violent penetrating injury and how the risk of adverse outcomes for survivors differs by injury type (stabbing vs. gunshot wound).

METHODS

This retrospective study was performed using a cohort of patients presenting to the Boston Medical Center emergency department for a penetrating injury due to community violence between 2006 and 2016. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the risk of all-cause mortality and violent reinjury within 3 years after surviving a penetrating injury.

RESULTS

Of the 4,280 survivors of the initial violent penetrating injury, there were 88 deaths (2.1%) and 568 violent reinjuries (13.3%) within 3 years. Compared with gunshot wound victims, stab wound victims were 31% less likely to be reinjured with a gunshot wound (HR, 0.69; 95% CI, 0.51–0.93), 72% more likely to be reinjured with a stab wound (HR, 1.72; 95% CI, 1.21–2.43), and 49% more likely to be reinjured by assault (HR, 1.49; 95% CI, 1.14–1.94). While survivors of stabbing and firearm injuries were equally at risk for 3-year all-cause mortality, stab wound victims were 3.75 times more likely to die by a drug/alcohol overdose (HR, 3.75; 95% CI, 1.11–20.65).

CONCLUSION

Patients surviving a stab wound have a significantly higher risk of violent reinjury by stabbing or assault, and risk of death by drug/alcohol overdose. Hospital-based violence intervention programs with similar patient populations should explore options to expand partnerships with drug treatment programs. These results illustrate two distinct populations of victims of violence―gunshot victims and stabbing/assault victims―with separate risk factors and outcomes, mediated by substance use disorder.

LEVEL OF EVIDENCE

Prognostic and Epidemiologic; level III.
Psychosocial interventions for people with a first episode psychosis: between tradition and innovation
Authors: Singh Swaran P. , Mohan Mohapradeep , Giacco Domenico
Published: July 2021

Purpose of review

Assessing recent evidence on psychosocial interventions for people with first episode psychosis (FEP).

Recent findings

Family interventions (FI) reduce relapse rates, whilst cognitive behavioural therapy (CBT) shows a moderate effect in improving positive psychotic symptoms. Vocational interventions (VI) appear to be worthy of implementation within early intervention for psychosis (EIP) teams, but it is still unclear what is the most cost-effective strategy for their delivery. Promising interventions, which need more careful evaluation, focus on substance misuse, physical health comorbidities, improvement of social participation, peer support and the potential of new technologies.

The first five years after the onset of psychotic symptoms are a ‘critical period’ in which psychosocial interventions can be particularly influential in determining prognosis. Traditional EIP interventions have different effectiveness profiles, i.e., FI reduce relapse rates, CBT has a moderate effectiveness on overall and positive symptoms and VI can improve educational and employment-related functioning. Newer interventions show promise on important targets for FEP treatment but require higher-quality evaluations. Decisions on which interventions to implement within EIP teams should be informed by high-quality evidence, but difficult choices will have to be made based on costs, professionals and technologies available, and local priorities.
Protocol for a pharmacogenetic study of antidepressants: characterization of drug-metabolizing profiles of cytochromes CYP2D6 and CYP2C19 in a Sardinian population of patients with major depressive disorder
Authors: Pinna Marco , Manchia Mirko , Pisanu Claudia , Pinna Federica , Paribello Pasquale , Carta Andrea , Meloni Anna , Conversano Claudio , Del Zompo Maria , Mola Francesco , Squassina Alessio , Carpiniello Bernardo
Published: July 2021

The effectiveness of antidepressants shows high interindividual variability ranging from full symptomatologic remission to treatment-resistant depression. Many factors can determine the variation in the clinical response, but a fundamental role is played by genetic variation within the genes encoding for the enzymes most involved in the metabolism of antidepressant drugs: the CYP2D6 and CYP2C19 isoforms of the cytochrome P450 system. This study is poised to clarify whether the different metabolizing phenotypes related to CYP2D6 and CYP2C19 could have an impact on the clinical efficacy of antidepressants and whether the frequency of these phenotypes of metabolization shows differences in the population of Sardinian patients compared to other Caucasian populations. The sample is being recruited from patients followed-up and treated at the Psychiatric Unit of the Department of Medical Science and Public Health, University of Cagliari and the University Hospital Agency of Cagliari (Italy). The study design includes three approaches: (1) a pharmacogenetic analysis of 80 patients diagnosed with MDD resistant to antidepressant treatment compared to 80 clinically responsive or remitted patients; (2) a prospective arm (N = 30) of the study where we will test the impact of genetic variation within the CYP2D6 and CYP2C19 genes on clinical response to antidepressants and on their serum levels and (3) the assessment of the socio-economic impact of antidepressant therapies, and estimation of the cost-effectiveness of the pharmacogenetic test based on CYP genes.
Museum genomics reveals the Xerces blue butterfly (Glaucopsyche xerces) was a distinct species driven to extinction
Authors: Grewe Felix , Kronforst Marcus R. , Pierce Naomi E. , Moreau Corrie S.
Published: July 2021

The last Xerces blue butterfly was seen in the early 1940s, and its extinction is credited to human urban development. This butterfly has become a North American icon for insect conservation, but some have questioned whether it was truly a distinct species, or simply an isolated population of another living species. To address this question, we leveraged next-generation sequencing using a 93-year-old museum specimen. We applied a genome skimming strategy that aimed for the organellar genome and high-copy fractions of the nuclear genome by a shallow sequencing approach. From these data, we were able to recover over 200 million nucleotides, which assembled into several phylogenetically informative markers and the near-complete mitochondrial genome. From our phylogenetic analyses and haplotype network analysis we conclude that the Xerces blue butterfly was a distinct species driven to extinction.
Scalable control of developmental timetables by epigenetic switching networks
Authors: Nguyen Phuc , Pease Nicholas A. , Kueh Hao Yuan
Published: July 2021

During development, progenitor cells follow timetables for differentiation that span many cell generations. These developmental timetables are robustly encoded by the embryo, yet scalably adjustable by evolution, facilitating variation in organism size and form. Epigenetic switches, involving rate-limiting activation steps at regulatory gene loci, control gene activation timing in diverse contexts, and could profoundly impact the dynamics of gene regulatory networks controlling developmental lineage specification. Here, we develop a mathematical framework to model regulatory networks with genes controlled by epigenetic switches. Using this framework, we show that such epigenetic switching networks uphold developmental timetables that robustly span many cell generations, and enable the generation of differentiated cells in precisely defined numbers and fractions. Changes to epigenetic switching networks can readily alter the timing of developmental events within a timetable, or alter the overall speed at which timetables unfold, enabling scalable control over differentiated population sizes. With their robust, yet flexibly adjustable nature, epigenetic switching networks could represent central targets on which evolution acts to manufacture diversity in organism size and form.
Back to the bones: do muscle area assessment techniques predict functional evolution across a macroevolutionary radiation?
Authors: Bates Karl T. , Wang Linjie , Dempsey Matthew , Broyde Sarah , Fagan Michael J. , Cox Philip G.
Published: July 2021

Measures of attachment or accommodation area on the skeleton are a popular means of rapidly generating estimates of muscle proportions and functional performance for use in large-scale macroevolutionary studies. Herein, we provide the first evaluation of the accuracy of these muscle area assessment (MAA) techniques for estimating muscle proportions, force outputs and bone loading in a comparative macroevolutionary context using the rodent masticatory system as a case study. We find that MAA approaches perform poorly, yielding large absolute errors in muscle properties, bite force and particularly bone stress. Perhaps more fundamentally, these methods regularly fail to correctly capture many qualitative differences between rodent morphotypes, particularly in stress patterns in finite-element models. Our findings cast doubts on the validity of these approaches as means to provide input data for biomechanical models applied to understand functional transitions in the fossil record, and perhaps even in taxon-rich statistical models that examine broad-scale macroevolutionary patterns. We suggest that future work should go back to the bones to test if correlations between attachment area and muscle size within homologous muscles across a large number of species yield strong predictive relationships that could be used to deliver more accurate predictions for macroevolutionary and functional studies.
Cellulosimicrobium composti sp. nov., a thermophilic bacterium isolated from compost
Authors: Hu Lin , Xia Mengli , Gao Xi , Huo Yi-Xin , Yang Yu
Published: July 2021

A Gram-stain-positive, yellow-pigmented, non-motile actinobacterial strain, designated as BIT-GX5T, was isolated from a sesame husks compost collected in Beijing, PR China. This bacterium was found to be able to grow in the temperature range from 16 to 50 °C and had an optimal growth temperature at 45 °C. Its taxonomic position was analysed using a polyphasic approach. The 16S rRNA gene sequence (1482 bp) of strain BIT-GX5T was most similar to

Cellulosimicrobium funkei

ATCC BAA-886T (99.45%),

Cellulosimicrobium cellulans

LMG 16121T (99.17%) and

Cellulosimicrobium marinum

RS-7-4T (98.75%). The results of phylogenetic analyses, based on the 16S rRNA gene, concatenated sequences of five housekeeping genes (gyrB, rpoB, recA, atpD and trpB) and genome sequences, placed strain BIT-GX5T in a separate lineage among the genus

Cellulosimicrobium

within the family

Promicromonosporaceae

. The major polar lipids of strain BIT-GX5T were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, aminophospholipid and aminolipid. The major isoprenoid quinone was MK-9(H4), while the cell-wall sugars were galactose, rhamnose, glucose and mannose. The peptidoglycan type was A4α l-Lys–d-Ser–d-Asp. The major fatty acids were anteiso-C15:0 and iso-C15: 0, which were similar to other members in the genus Cellulosimicrobium. Results of in silico DNA–DNA hybridization and average nucleotide identity calculations plus physiological and biochemical tests exhibited the genotypic and phenotypic differentiation of strain BIT-GX5T from the other members of the genus

Cellulosimicrobium

. Therefore, strain BIT-GX5T is considered to represent a novel species within the genus

Cellulosimicrobium

, for which the name Cellulosimicrobium composti sp. nov. is proposed. The type strain is BIT-GX5T (= CGMCC 1.17687T = KCTC 49391T).
Unveiling Mutation Effects on the Structural Dynamics of the Main Protease from SARS-CoV-2 with Hybrid Simulation Methods
Authors: Gasparini P , Philot EA , Magro AJ , Mattos JC , Torres-Bonfim NESM , Kliousoff A , Quiroz RCN , Perahia D , Scott AL
Published: July 2021

The main protease of SARS-CoV-2 (called Mpro or 3CLpro) is essential for processing polyproteins encoded by viral RNA. Macromolecules adopt several favored conformations in solution depending on their structure and shape, determining their dynamics and function. Integrated methods combining the lowest-frequency movements obtained by Normal Mode Analysis (NMA), and the faster movements from Molecular Dynamics (MD), and data from biophysical techniques, are necessary to establish the correlation between complex structural dynamics of macromolecules and their function. In this article, we used a hybrid simulation method to sample the conformational space to characterize the structural dynamics and global motions of WT SARS-CoV-2 Mpro and 48 mutants, including several mutations that appear in P.1, B.1.1.7, B.1.351, B.1.525 and B.1.429+B.1.427 variants. Integrated Hybrid methods combining NMA and MD have been useful to study the correlation between the complex structural dynamics of macromolecules and their functioning mechanisms. Here, we applied this hybrid approach to elucidate the effects of mutation in the structural dynamics of SARS-CoV-2 Mpro, considering their flexibility, solvent accessible surface area analyses, global movements, and catalytic dyad distance. Furthermore, some mutants showed significant changes in their structural dynamics and conformation, which could lead to distinct functional properties.

Highlights

Single surface mutations lead to changes in Mpro structural dynamics.

Mutants can be more stable than WT according to the structural dynamics properties.

Mpromutants can present a distinct functionality in relation to the wild-type.

Potential viral markers for more pathogenic or transmissible SARS-CoV-2 variants.
Rapid visual CRISPR assay: a naked-eye colorimetric detection method for nucleic acids based on CRISPR/Cas12a and convolutional neural network
Authors: Xie Shengsong , Tao Dagang , Fu Yuhua , Xu Bingrong , Tang You , Steinaa Lucilla , Hemmink Johanneke D , Pan Wenya , Huang Xin , Nie Xiongwei , Zhao Changzhi , Ruan Jinxue , Zhang Yi , Han Jianlin , Fu Liangliang , Ma Yunlong , Li Xinyun , Liu Xiaolei , Zhao Shuhong
Published: July 2021

Rapid diagnosis based on naked-eye colorimetric detection remains challenging, but it could build new capacities for molecular point-of-care testing (POCT). In this study, we evaluated the performance of 16 types of single-stranded DNA-fluorophore-quencher (ssDNA-FQ) reporters for use with CRISPR/Cas12a based visual colorimetric assays. Among them, 9 ssDNA-FQ reporters were found to be suitable for direct visual colorimetric detection, with especially very strong performance using ROX-labeled reporters. We optimized the reaction concentrations of these ssDNA-FQ reporters for naked-eye read-out of assay results (no transducing component required for visualization). Subsequently, we developed a convolutional neural network algorithm standardize and to automate the analytical colorimetric assessment of images and integrated this into the MagicEye mobile phone software. A field-deployable assay platform named RApid VIsual CRISPR (RAVI-CRISPR) based on a ROX-labeled reporter with isothermal amplification and CRISPR/Cas12a targeting was established. We deployed RAVI-CRISPR in a single tube towards an instrument-less colorimetric POCT format that requires only a portable rechargeable hand warmer for incubation. The RAVI-CRISPR was successfully used for the single-copy detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and African swine fever virus (ASFV). Our study demonstrates this novel RAVI-CRISPR system for distinguishing different pathogenic nucleic acid targets with high specificity and sensitivity as the simplest-to-date platform for rapid pen-side testing.