bluuebunny/crossref_metadata_2025 huggingface dataset:
Diffuse Pulmonary Meningotheliomatosis: A Case Report
Authors: Forsythe M L , Abdelsadek O A , Prasai K , Raval P A , Krantz S B , Shah R D , Groth J V
Published: November 2022

Introduction/Objective

Diffuse pulmonary meningotheliomatosis (DPM) is a pulmonary disease characterized by the presence of widespread bilateral minute pulmonary meningothelial-like nodules (MPMNs). It is exceedingly rare and predominantly seen in females. The nodules are typically asymptomatic and detected incidentally on imaging.

Methods/Case Report

We present a case of a 57-year-old woman with a history of chronic cough and CT imaging findings of bilateral multiple ground-glass nodules. Wedge resections from the right upper and right lower lobes were obtained, which revealed gross changes suggestive of interstitial lung disease. Histologic evaluation of the wedges showed similar morphology, consisting of discrete areas with variable interstitial expansion of the stroma with ovoid/spindle cells, collagen, elastosis, and mild chronic inflammatory cells, in a somewhat perivascular pattern. Some areas were also cystic. This appeared in a background of emphysematous change and focal foreign body giant cell reaction to non-polarizable material. Immunohistochemical stains were diffusely positive for vimentin, EMA , and PR, and CD163 highlighted increased cells that were S100 and CD1a negative. Additionally, the ovoid/spindle cells were negative for desmin, SMM, HMB-45, HHV8, pan-CK, chromogranin, and multiplex SOX10-MART1.

Results (if a Case Study enter NA)

NA

Conclusion

Diffuse pulmonary meningotheliomatosis is a rare entity that requires sufficient histological evaluation to identify the ovoid/spindle cell component histologically and immunohistochemically. This disease should be considered in the differential for cases of diffuse interstitial pulmonary infiltrates. Few cases have been reported in the literature, requiring further research to understand the mechanisms of this disease and its clinical significance.
Lady Windermere Syndrome: Historical Perspective and Report of a Rare Case
Authors: Al-kharouf I , Abdo M E , Hamza A
Published: November 2022

Introduction/Objective

Lady Windermere syndrome refers to Mycobacterium avium complex (MAC) pulmonary disease with an isolated lingular or middle lobe pattern of involvement. This is thought to be due to habitual suppression of the cough voluntarily. Typical demographics are that of elderly female patient. Although the etiology remains unclear high prevalence of pectus excavatum, scoliosis and mitral valve prolapse has also been noted in these patients. The purpose of this report this to describe a case of this syndrome.

Methods/Case Report

A 64-year-old female with a history of breast carcinoma status post bilateral mastectomies, and thyroid papillary microcarcinoma, status post thyroidectomy, presented with hemoptysis. Clinically and radiological findings were consistent with pneumonia which improved but did not completely resolve following antibiotic treatment. Computerized tomography (CT) revealed progressive infiltrates and bronchoscopy cultures grew Mycobacterium avium complex (MAC). Repeat antibiotic therapy resulted in only marginal improvement. Repeat CT showed diffuse bronchiectatic changes with scattered nodularity and tree-in-bud opacities, with majority of involvement in the right middle lobe and lingula. Multiple interventions were employed to ameliorate the patient’s condition including a positive expiratory pressure device, gastroesophageal reflux disease (GERD) precautions and combinations of 2 drug therapies without significant improvement in her condition. It was ultimately decided that she may benefit from a right middle lobectomy. Histologic sections from the lobectomy specimen showed necrotizing and non-necrotizing granulomatous inflammation and bronchiolectasis. Rare acid-fast microorganisms were identified on AFB special satin. Lady Windermere syndrome was suggested in the diagnostic comment after expert consultation. Patient’s symptoms improved after surgery and additional samples show no growth of MAC.

Results (if a Case Study enter NA)

NA

Conclusion

Although rendering a definite diagnosis is challenging in such cases, the constellation of clinical, radiologic, and histologic finding can be used to raise the possibility of Lady Windermere syndrome.
Cryptococcus Infection Mimicking Lipoid Pneumonia in a Lung Biopsy
Authors: Walkenhorst M , Hamza A
Published: November 2022

Introduction/Objective

Lipoid pneumonia is a non-infectious, rare entity which results from accumulation of exogenous or endogenous lipids in the lungs. It appears as intraalveolar macrophages filled with lipids in the form of fine spherical vacuoles. Cryptococcosis can also appear as vacuolated macrophages filled with yeasts. At low magnification, the distinction is very difficult. The co-existence of the two entities is noted in literature but is exceedingly rare.

Methods/Case Report

A 33-year-old male, status post renal and pancreatic transplant, on chronic immunosuppression therapy presented with dysphagia. Imaging studies showed cavitary and non-cavitary nodules, patchy, confluent consolidations in the bilateral lungs, and a patulous, debris filled esophagus. This raised the possibility of atypical infections as well as aspiration. Biopsy of a right lower lobe lung lesion was performed. Histology demonstrated fibrotic lung parenchyma with vacuolated histiocytes containing small spherical substances. The differential diagnosis included Cryptococcus infection versus exogenous lipoid pneumonia, both of which were consistent with clinical and radiologic findings. Few, scattered foreign body giant cells were found. Additionally, GMS and mucicarmine stains were positive in the small spheres within the macrophages. The final diagnosis of lung parenchyma with numerous yeast forms, morphologically consistent with cryptococcus species was rendered. The patient was additionally found to have esophageal candidiasis. Concurrent lipoid pneumonia was considered unlikely based on the patient's history of immunosuppression (which made infection a much more likely etiology) and paucity of foreign body giant cell reaction.

Results (if a Case Study enter NA)

NA

Conclusion

This case highlights the importance of knowledge of rare entities and correlation with clinical and radiologic findings in arriving at an accurate diagnosis.
The Spectrum of Pulmonary Histomorphology Changes in COVID-19 Cases
Authors: Ravikumar V , Cool C , Jing J
Published: November 2022

Introduction/Objective

Pulmonary specimens following COVID-19 virus infection demonstrate a spectrum of pulmonary histomorphology. Six patients with a history of COVID-19 infection are summarized in this review. The purpose of our study is to elucidate any possible correlations between clinical, laboratory, radiographic, and pathologic findings in COVID-19 patients. Further, we aim to characterize both non-specific and specific histomorphology and cytomorphology in COVID-19 patients.

Methods/Case Report

Six patients with known COVID-19 infection and lung biopsies/resections are identified. A chart review is performed to collect clinical histories, the results of COVID-19 PCR testing, radiographic impressions, pathologic interpretations of histology, and clinical outcomes. Information is summarized and tabulated.

Results (if a Case Study enter NA)

The most common, non-specific histological findings are focal/diffuse acute lung injury, organizing lung injury, or a combination of both patterns. Unique features of COVID-19 infection are identified in three cases, which illustrate viral cytopathic changes within hyperplastic pneumocytes. These include basophilic, vacuolated, granular cytoplasm and variably sized cytoplasmic/nuclear inclusions. Virus-loaded pneumocytes are typically identified in the organizing phase, and rarely in the acute lung injury phase. Immunohistochemical staining of anti-nuclear capsule antibody with appropriate controls shows focal positive staining in one case. SARS-CoV-2 PCR is positive in formalin-fixed paraffin-embedded (FFPE) tissue, while a serum PCR assay is negative.

Conclusion

The severity of clinical symptoms and clinical outcome are unrelated to the degree of lung involvement. Viral cytopathic changes are identified in three cases, with these specific findings associated with the organizing phase of lung injury, and either concurrent PCR positivity or positive immunohistochemical staining.
The Number of Calcium Oxalate Deposits Significantly Correlate with Elevated Serum Creatinine Levels in Calcium Oxalate Nephropathy
Authors: Kumar S , Zhang P
Published: November 2022

Introduction/Objective

Calcium oxalate nephropathy is defined as acute and/or chronic decrease in renal function due to deposition of calcium oxalate crystals in renal tubules leading to acute tubular injury, acute or chronic interstitial nephritis, and elevated serum creatinine levels. However, the correlation between serum creatinine (SCr) levels and the number of calcium oxalate deposits has not been well described in the literature.

Methods/Case Report

Eight controls with mild to moderate acute tubular injury and 10 cases with calcium oxalate nephropathy (calcium group) were selected for the study. The patient’s SCr values were obtained from electronic medical records and the number of polarizable calcium oxalate crystal deposits in the lumen of proximal tubules seen on Hematoxylin & Eosin stained slides at 40x high power field were recorded for each biopsy. Umpired student T-test was used to compare the two groups. Linear regression analysis was used to correlate SCr and the number of calcium oxalate deposits.

Results (if a Case Study enter NA)

Mean ages were not significantly different between two groups (49 ± 8 years in controls and 64 ± 6 years in calcium group). SCr was significantly higher in the calcium group (5.97 ± 0.68 mg/dl*) than in the control group (2.59 ± 0.37 mg/dl). No calcium oxalate deposits were seen in any of the controls, but the number of calcium oxalate deposits ranged from 3 to 7 in the calcium group (Table 1). In our study, we found a significant linear correlation between SCr and the number of crystals/high power field, when all cases were taken together (r value = 0.783, p value = 0.0002*).

Conclusion

Our data suggest that there is a direct association between the number of calcium oxalate crystals in proximal tubules with the severity of renal dysfunction. Although the etiologies for calcium oxalate nephropathy can be multifactorial, counting the deposit number on renal biopsies is simple method to predict SCr levels.
Continuing Profound Impact of Continued Education Sessions on Blood Bank Specimen Labeling Years Later at the Veteran Affairs Medical Center
Authors: Petersen J M , Jhala D , Patel V
Published: November 2022

Introduction/Objective

Proper patient identification is a critical safety element for transfusion medicine, particularly for the prevention of acute hemolytic transfusion reactions (AHTR). Mislabeled specimens have been documented to carry an increased risk of patient misidentification. Therefore, the submission of a mislabeled specimen to the blood bank generally results in a specimen rejection with a redraw. At the Philadelphia Veteran Affairs Medical Center, an identification bracelet with alphanumeric code is used to help improve transfusion safety but also has additional patient labeling requirements. The redrawing of blood bank specimens poses risks in phlebotomy, and a quality improvement initiative was previously undertaken to educate staff on proper blood specimen and band labeling and usage to prevent labeling errors, improve safety in patient care, and reduce intended redraws.

Methods/Case Report

Colorful laminated posters delineating the labeling requirements and process for blood bank specimens collected using the blood bank system were made and distributed at the time of in-service training by the blood bank in 2017 to the areas of the hospital whereby errors had been noted to occur in the past. The dedicated in-service training was repeated prior to the change in the identification blood band from the Hollister Ident-ATM Blood Recipient Band (Precision Diagnostics Corporation, Valencia CA) to the Typenex Blood Bands (Typenex Medical, Chicago IL) on 11/12/2019. As part of the quality metrics of the blood bank, blood bank specimen labeling errors was tracked from 2017 to track the persistence of the effect of the initial training.

Results (if a Case Study enter NA)

The percentage of properly labeled specimens as a percentage of total specimens increased after the in-service training; specifically, an increase from a low of 97% (December 2017) to a high of 99% (August 2018). The percentage of properly labeled specimens remains at the increased level of 99% and above even at the 4.5-year mark in mid-2022.

Conclusion

The continued availability of laminated educational posters on blood specimen labeling for the clinical service areas combined with initial in-service education can have lasting effects to improve the quality of care even years after the initial in-service education sessions.
Replicated Adsorption Technique used to Resolve ALX148 Interference in the Immunohematology Reference Laboratory
Authors: Flaws M , Hartman K , Geurkink C , Mullins D , Ha K , Zinni J G , Pahomi A
Published: November 2022

Introduction/Objective

Increased expression of CD47 by cancer cells inhibits macrophages' phagocytic activity through CD47-SIRPα interactions, allowing evasion of the innate immune system. Several drugs on the market have been developed to target this interaction, including monoclonal therapeutics and fusion proteins. ALX148 is a genetically engineered SIRPα fusion protein with an inactivated Fc portion. CD47 is expressed highly on red blood cells (RBC), resulting in strong interference in pre-transfusion compatibility testing of patients receiving ALX148. Consequently, trial patients are at increased risk of transfusion-related adverse events or delay of needed transfusion. Few resolutions of ALX148 interference to assess underlying alloantibody development have been reported. One such examiniation demonstrated x6 linear papain-treated RBC adsorptions removed ALX148 interference. This study aimed to replicate these findings.

Methods/Case Report

Three patients receiving combination ALX148 (dose 6.57-20mg/mL) and Azacitidine therapy with broad-reactive RBC antibody reactivity were selected. High volume alloadsorptions (8:1 RBC:plasma) were performed with papain-treated rr (ccdee) RBCs. Adsorptions were incubated at 37C for 10 minutes. Polyethylene glycol (PEG) was utilized in test tube indirect antiglobulin testing (IAT).

Results (if a Case Study enter NA)

Initial reactivity strength was 3-4+ at PEG-IAT and saline-IAT with a three-cell screening RBC reagent. Alloadsorbed plasma was non-reactive at IAT with a three-cell screening RBC reagent enhanced by PEG. Drug interference was removed following three times high volume papain-treated alloadsorption.

Conclusion

Cancer immunotherapies have transformed the standard of care in oncology. Despite the evident clinical success, the medical laboratory has been challenged with adapting to cancer drug therapies capable of causing interference in routine laboratory testing. Clinical trials of ALX148 are associated with interference in pre-transfusion compatibility testing. The use of extended phenotype matching for RBC transfusion can be utilized but incurs additional time and resources. These results suggest high volume linear papain RBC alloadsorptions may be incorporated into antibody resolution for patients receiving ALX148.
Highly Effective, Easy, & Simple Model for the Day-to-Day Monitoring of Blood Bank Inventory Leading to Successful Operations to Provide Blood Products in the Times of Blood Product Shortage Nationally Due to COVID-19 Pandemic
Authors: Patel V , Petersen J M , Jhala D
Published: November 2022

Introduction/Objective

Providing blood products in a timely manner is very important and is an integral part of the health care system to provide best patient care. Transfusion medicine services should be well prepared to respond to blood product demands in a timely manner. Due to the COVID-19 pandemic, all the transfusion medicine services nationally have been facing blood product shortages. A model was created in Pathology & Laboratory services (P&LMS) at the Corporal Michael J. Crescenz Veteran Affairs Medical Center (CMC VAMC) to communicate effectively to the patient care team to keep up with ongoing clinical care demands despite the national blood shortage.

Methods/Case Report

Transfusion medicine team at CMC VAMC communicated to patient care team about the national shortage of blood products. All blood requests were evaluated for appropriate usage of blood. Also, PACS (Peri Operative cells Savers) services was considered for Operating room for patient with major blood loss. Daily blood inventory was evaluated, closely monitored, and communicated to patient care team to meet the demands from Jan 16th, 2022, to April 11th, 2022. Importantly, P&LMS created a simple model where each blood product in reduction was recorded every morning and evening. This simple method of 24/7 real time monitoring of the supply of blood products helped tremendously in decision making for procedure prioritization based on clinical indications and contributed to the continued successful clinical operation.

Results (if a Case Study enter NA)

Procedures were successfully prioritized according to the blood supply. Simultaneously, there was no delay in issuing blood products as clinically needed. A significant amount of reduced inventory noted from Jan 16th, 2022, to April 11th, 2022; the average reduction was O+ 53% reduced and A+ 44% reduced.

Conclusion

By monitoring the day-to-day blood bank inventory effectively, P&LMS at CMC VAMC was able to support all the critical clinical needs by providing blood products in a timely manner. P&LMS services was able to reduce the wastage and was able to provide all the critical blood product without any significant delays by monitoring in Realtime. The value of collaborating and communicating to the patient care team cannot be understated as it is both simple and highly cost effective.
Resident Physician “Moonlighting” for On-call in Transfusion Medicine: Educational Impact and Preparedness for Practice
Authors: Bharadwaj H , Alhusseiny A , Pandiri M , Khan A , Jawale R , Johari V
Published: November 2022

Introduction/Objective

Resident physician moonlighting is controversial and uncommon in Pathology, usually limited to anatomic pathology grossing support. Due to an acute staffing shortage in our department, we offered senior AP/ CP residents in our program a “moonlighting” opportunity involving partnership with attendings to supervise junior residents for transfusion medicine on-call (TMO) . Given the conflicting claims of educational benefit and detriment of moonlighting, we sought to evaluate impact of TMO moonlighting activities on residents' educational experience and preparedness for clinical practice.

Methods/Case Report

Residents selected for moonlighting TMO were PGY-3/4, “exceeded expectations” on their transfusion medicine rotation and had taken resident TMO. After initial “boot camp” exercises involving common TMO scenarios, they were added to the attending on-call schedule with a fair financial incentive. They were the first resource and provided in-person support for the TMO resident. Attendings were available for consultation via a secure communications platform (phone and text). After one year, residents were surveyed regarding overall experience, sense of graduated responsibility, impact of financial incentive, preparedness for future practice, and impact on day- time service commitment. "Resident In-Service Examination" (RISE) score was used to estimate impact of TMO on medical knowledge.

Results (if a Case Study enter NA)

NA.

Conclusion

Four out of the five residents took the survey. All 4 responded “definite” for positive experience, feeling of graduated responsibility and preparedness for practice. Financial incentive was assessed favorably. No resident reported an adverse impact on their daytime service responsibility. The group median score on RISE transfusion medicine 2022 was 75th percentile with median increase in 10 percentile points. As pathology moves towards sub- specialty practice, working fluency in some areas such as TMO remains a necessity for smaller group practices. Our experience (albeit with a small group of residents) suggests that TMO moonlighting activities may better prepare the residents for this unmet need.
Comparative Sensitivity of Solid-Phase Versus PEG Enhancement Assays for Detection and Identification of Red Blood Cell Antibodies
Authors: Abdelmonem M , Dussaq A , Cai W , Tang M , Nguyen A , Papakonstantino K , Cabungan M , Yoshizuka S , Hollenhorst M
Published: November 2022

Introduction/Objective

Identifying antibodies to red blood cell (RBC) antigens is one of transfusion medicine’s most critical and challenging issues. There are 354 RBC antigens recognized by the International Society of Blood Transfusion. Accurate identification of clinically significant alloantibodies is imperative for identifying and preventing hemolytic transfusion reactions and hemolytic disease of the fetus and newborn. We compared the performance of the tube (polyethylene glycol–indirect antiglobulin test [PEG-IAT]) and solid-phase techniques for antibody identification.

Methods/Case Report

We performed a retrospective study on all antibody screens and identifications performed between 2007–2021 at Stanford Hospital. Over this period, 631,535 antibody screens were performed predominantly using an automated solid-phase technique. Subsequent antibody identification studies were performed using manual tube testing (PEG-IAT) and automated solid-phase techniques.

Results (if a Case Study enter NA)

Antibody screening resulted in 28,316 (4.5%) positive samples with at least one antibody. Antibody identification performed on both platforms identified 50 discordant [DMH1] samples. 8 anti-Jka, 2 anti-Jkb, 1 anti-S, and 1 anti-M were detected by automatic solid-phase technique but were not detected by PEG-IAT. 20 anti-E, 6 anti-K, 2 anti-Fya, 2 anti-c , 2 anti-C, 2 anti-Fyb, 1 anti-cE[DMH2] , 1 anti-e,1 anti-M, and 1 anti-S were detected by PEG-IAT but were negative by automated solid-phase technique. Anti-E had the least sensitivity (98.99%) in the automated solid-phase technique, while anti-Jkb had the least sensitivity (98.78%) in PEG-IAT.

Conclusion

This is the first robust 15-year study comparing methodologic sensitivity to detect clinically significant alloantibodies. The incidence of discordant results between the PEG-IAT and solid-phase technique was low. Among discordant samples, anti-Jka was commonly detected by solid-phase but not by PEG-IAT. In contrast, anti-E was commonly detected by PEG-IAT but not by the solid phase.
First Massive Transfusion Protocol (MTP) Implementation Proposal in Egypt
Authors: Abdelmonem M , Wasim H , Shedid M , Elhusseny A
Published: November 2022

Introduction/Objective

Massive transfusion is often defined as transfusion of adults with 10 or more of packed red blood cells units in 24 hours period or transfusion of 4 or more units of packed red blood cells (PRBCs) in one hour when on-going need for more transfusion is foreseeable. Massive transfusion protocol in children is defined as transfusion of >40 mL/kg. Massive transfusion protocol (MTP) is a vital element of damage control resuscitation and provides a coordinated clinical response to hemorrhage in patients requiring massive blood transfusions after hospital admission. Hemorrhage is the most common cause of death within the first hour of arrival to the trauma center.

Methods/Case Report

This study aims to develop and establish the first massive protocol in Egypt to provide a consistent treatment for blood transfusion for trauma patients that will Reduce delay in ordering and administering blood products and Deliver a reasonable ratio of plasma to red blood cells. The protocol will be first implemented in a military hospital in Egypt. Developing the massive transfusion protocol will allow the practitioners to follow algorithm for rapid replacement of blood products using uncrossmatched packed red blood cells, Plasma, platelets and cryoprecipitate if necessary. Adopting the American Association of Blood Banks (AABB) and the American College of Surgeons (ACS) guidelines are the best practice around the world. The Protocol will be developed by multidisciplinary committee engagement, Blood bank, Diagnostic laboratory and Clinical care areas (OR, ER, ICU, OBS).

Results (if a Case Study enter NA)

The massive transfusion protocol ratio will be 3:2 (RBC: FFP) and one units of platelets for every 6 units of RBC. according to American College of Surgeons (ACS) guidelines the ratio should be 1:1 to 1:2 (RBC: FFP). The committee established defined criteria for MTP activation and termination. The delivery time of the blood products should be between 5-10 minutes. Administration of tranexamic acid to inhibit plasminogen activation and stabilize the clot.

Conclusion

The Developing and Implementing MTP in Egypt will provide reduction in mortality for trauma and uncontrolled hemorrhage patients. Once implemented, we will regularly evaluate the use and efficacy of the MTP to ensure positive patient outcomes., the MTP will be evaluated to ensure best practice.
Pre-ataxic loss of intrinsic plasticity and motor learning in a mouse model of SCA1
Authors: Osório Catarina , White Joshua J , Lu Heiling , Beekhof Gerrit C , Fiocchi Francesca Romana , Andriessen Charlotte A , Dijkhuizen Stephanie , Post Laura , Schonewille Martijn
Published: November 2022

Spinocerebellar ataxias are neurodegenerative diseases, the hallmark symptom of which is the development of ataxia due to cerebellar dysfunction. Purkinje cells, the principal neurons of the cerebellar cortex, are the main cells affected in these disorders, but the sequence of pathological events leading to their dysfunction is poorly understood. Understanding the origins of Purkinje cells dysfunction before it manifests is imperative to interpret the functional and behavioural consequences of cerebellar-related disorders, providing an optimal timeline for therapeutic interventions.

Here, we report the cascade of events leading to Purkinje cells dysfunction before the onset of ataxia in a mouse model of spinocerebellar ataxia 1 (SCA1). Spatiotemporal characterization of the ATXN1[82Q] SCA1 mouse model revealed high levels of the mutant ATXN1[82Q] weeks before the onset of ataxia. The expression of the toxic protein first caused a reduction of Purkinje cells intrinsic excitability, which was followed by atrophy of Purkinje cells dendrite arborization and aberrant glutamatergic signalling, finally leading to disruption of Purkinje cells innervation of climbing fibres and loss of intrinsic plasticity of Purkinje cells. Functionally, we found that deficits in eyeblink conditioning, a form of cerebellum-dependent motor learning, precede the onset of ataxia, matching the timeline of climbing fibre degeneration and reduced intrinsic plasticity.

Together, our results suggest that abnormal synaptic signalling and intrinsic plasticity during the pre-ataxia stage of spinocerebellar ataxias underlie an aberrant cerebellar circuitry that anticipates the full extent of the disease severity. Furthermore, our work indicates the potential for eyeblink conditioning to be used as a sensitive tool to detect early cerebellar dysfunction as a sign of future disease.
PPM1G promotes the progression of lung adenocarcinoma by inhibiting p38 activation via dephosphorylation of MEK6
Authors: Chen Jingying , Li Jizhuo , Sun Hong , Hu Tianyi , Wang Yameng , Kang Guoqi , Cao Mingya , Li Xia
Published: November 2022

The p38 MAP kinase (MAPK) signaling pathway is a key signal transduction cascade that cancer cells employ to sense and adapt to a plethora of environmental stimuli and has attracted much attention as a promising target for cancer therapy. Although the kinases that phosphorylate p38 have been extensively studied, the negative regulation of p38 phosphorylation remains to be elucidated. Here, we found that PPM1G was highly expressed in lung adenocarcinoma (LUAD) compared to normal tissues, and higher levels of PPM1G were observed in adverse staged LUAD. Furthermore, the higher levels of PPM1G were highly correlated with poor prognosis, according to the Cancer Genome Atlas cohort. Most importantly, we identified phospho-MEK6 as a direct substrate of PPM1G. PPM1G, a metal-dependent protein phosphatase family phosphatase, could reduce p38 phosphorylation via MEK6 dephosphorylation and contribute to the proliferation, invasion and metastasis of LUAD. Our study highlighted the essential role of PPM1G in LUAD and shed new light on unveiling the regulation of p38 activity via direct dephosphorylation of MEK6 in malignant transformation. Together, this study provides new insight into the complexity of regulating the versatile p38 signaling and suggests new directions in intervening in p38 MAPK signaling.
Exhaled Mycobacterium tuberculosis Predicts Incident Infection in Household Contacts
Authors: Williams Caroline M , Muhammad Abdul K , Sambou Basil , Bojang Adama , Jobe Alhaji , Daffeh Georgetta K , Owolabi Olumuyiwa , Pan Daniel , Pareek Manish , Barer Michael R , Sutherland Jayne S , Haldar Pranabashis
Published: November 2022

Background

Halting transmission of Mycobacterium tuberculosis (Mtb) by identifying infectious individuals early is key to eradicating tuberculosis (TB). Here we evaluate face mask sampling as a tool for stratifying the infection risk of individuals with pulmonary TB (PTB) to their household contacts.

Methods

Forty-six sputum-positive PTB patients in The Gambia (August 2016–November 2017) consented to mask sampling prior to commencing treatment. Incident Mtb infection was defined in 181 of their 217 household contacts as QuantiFERON conversion or an increase in interferon-γ of ≥1 IU/mL, 6 months after index diagnosis. Multilevel mixed-effects logistical regression analysis with cluster adjustment by household was used to identify predictors of incident infection.

Results

Mtb was detected in 91% of PTB mask samples with high variation in IS6110 copies (5.3 × 102 to 1.2 × 107). A high mask Mtb level (≥20 000 IS6110 copies) was observed in 45% of cases and was independently associated with increased likelihood of incident Mtb infection in contacts (adjusted odds ratio, 3.20 [95% confidence interval, 1.26–8.12]; P = .01), compared with cases having low-positive/negative mask Mtb levels. Mask Mtb level was a better predictor of incident Mtb infection than sputum bacillary load, chest radiographic characteristics, or sleeping proximity.

Conclusions

Mask sampling offers a sensitive and noninvasive tool to support the stratification of individuals who are most infectious in high-TB-burden settings. Our approach can provide better insight into community transmission in complex environments.
Drought, wildfire and forest transformation: characterizing trailing edge forests in the eastern Cascade Range, Washington, USA
Authors: Meigs Garrett W , Case Michael J , Churchill Derek J , Hersey Charles M , Jeronimo Sean M A , Smith L Annie C
Published: November 2022

Climate change and the compounding effects of drought and wildfire are catalyzing rapid ecosystem changes throughout the world. Relatively dry, trailing edge (TE) forests are especially vulnerable to ecological transformation when tree regeneration is moisture-limited following high-severity fire. Here, we illustrate the potential landscape-scale impacts of changing disturbance regimes by focusing on TE forests in the eastern Cascades of Washington, USA. Our specific objectives were to: (1) map TE forests based on climatic water deficit and forest cover; (2) characterize the composition, structure, and ownership of TE and non-TE forests; (3) quantify recent fire activity in TE and non-TE forests; (4) identify locations of potential forest loss where recent fires have burned severely in TE forests. Across the study area, TE forests encompassed 387 000 ha, representing a substantial portion (21 per cent) of the total forested landscape. TE forests generally were characterized by dry, mixed-conifer forest types with more open structure and less biomass than non-TE forests. The structural and compositional conditions within TE forests make them ideal locations for management strategies designed to enhance landscape resilience and sustain fire-resistant trees. TE forestland ownership is diverse (35 per cent federal, 19 per cent Tribal, 16 per cent Washington State, 14 per cent private non-industrial and 13 per cent private industrial), indicating that successful land management will require collaboration among numerous partners. Recent wildfires (1984–2020) cumulatively covered 84 300 ha (22 per cent) of TE forests and 363 500 ha (25 per cent) of non-TE forests. TE forests experienced less high-severity fire than non-TE forests (39 per cent vs. 46 per cent, respectively). Recent high-severity fire effects in TE forests occurred primarily in the northern portion of the study region, reflecting the distribution of individual large fires. By quantifying the variability of TE forests and their recent fire activity, this study supports adaptive management strategies for landscape restoration, post-disturbance reforestation and climate adaptation.
An empirical review of ICES reference points
Authors: Silvar-Viladomiu Paula , Batts Luke , Minto Cóilín , Miller David , Lordan Colm
Published: November 2022

The International Council for the Exploration of the Sea (ICES) has provided scientific stock advice based on reference points to manage fisheries in the North Atlantic Ocean and adjacent seas for decades. ICES advice integrates the precautionary approach with the objective of achieving maximum sustainable yield. Here, we examine ICES reference point evolution over the last 25 yr and provide a comprehensive empirical review of current ICES reference points for data-rich stocks (Category 1; 79 stocks). The consistency of reference point estimation with the ICES guidelines is evaluated. We demonstrate: (1) how the framework has evolved over time in an intergovernmental setting, (2) that multiple precautionary components and sources of stochasticity are included, (3) that the relationship and historical context of stock size and recruitment are crucial for non-proxy reference points, (4) that reference points are reviewed frequently, taking into account fluctuations and multiple sources of variability, (5) that there are occasional inconsistencies with the guidelines, and (6) that more comprehensive and clearer documentation is needed. Simplifying the stock-recruit typology and developing quantitative criteria would assist with this critically important classification. We recommend a well-documented, transparent, and reproducible framework, and periodic syntheses comparing applications across all stocks.
Contrastive learning-based image retrieval for automatic recognition of in situ marine plankton images
Authors: Yang Zhenyu , Li Jianping , Chen Tao , Pu Yuchun , Feng Zhenghui
Published: November 2022

Automatic recognition of in situ marine plankton images has long been treated as an image classification problem in machine learning. However, the deep learning-based classifiers are far from robust when used for predicting actual oceanic data that inevitably has distributional and compositional variations from their training sets. This paper proposes a novel image retrieval-based framework for plankton image recognition, within which supervised contrastive learning is used to train a feature extractor for better image representation, and similarity between the input and a gallery of reference images is compared to determine the identity of queries. We construct a dataset of high-quality in situ dark-field images of plankton and suspended particles to train and test the proposed retrieval model. Experimental results show that the image retrieval method has achieved excellent recognition performance similar to the state-of-the-art classification models on a very imbalanced closed-set, and also exhibited better generalizability in dealing with dataset shift and out-of-distribution issues. In addition, the image retrieval method has also demonstrated great architectural flexibility, bringing practical convenience for its adaptation to complex marine application scenarios. This new recognition framework is expected to enable real-time in situ observation of marine plankton in the actual oceanic underwater environment in the near future.
Prediabetes and risk of active tuberculosis: a cohort study from Northern Taiwan
Authors: Ko Tsun-Hao , Chang Yi-Cheng , Chang Chia-Hsuin , Liao Karen Chia-Wen , Magee Matthew J , Lin Hsien-Ho
Published: November 2022

Background

Diabetes mellitus (DM) is a well-established risk factor for active tuberculosis (TB) infection. Despite the worldwide rapid increase in the prevalence of prediabetes, its impact on the risk of active TB remains largely unknown. This study aimed to investigate the relationship between prediabetes and risk of active TB in a large cohort study.

Methods

A total of 119 352 participants were screened from a community-based health screening programme in Northern Taiwan. Diabetes mellitus and prediabetes were defined by baseline fasting plasma glucose (FPG) and prescription of anti-diabetic drugs. Incident cases of active TB were identified from the National Tuberculosis Registry. Kaplan–Meier curves and Cox regression analysis were employed to estimate the hazard ratios for prediabetes and DM compared with normoglycaemia. Spline regression was performed to investigate the dose-response relationship between FPG level and risk of TB disease.

Results

At baseline, 27 404 (22.96%) participants had prediabetes and 10 943 (9.17%) participants had DM. After an average follow-up of 7.2 years, 322 TB cases occurred. The adjusted hazard ratio of developing active TB disease was 0.73 [95% confidence interval (CI) 0.55–0.97] for prediabetic and 1.48 (95% CI 1.11–1.98) for diabetic participants compared with normoglycaemic individuals. Spline regression revealed a U-shaped association between FPG level and risk of active TB disease, with the lowest risk at FPG around110 mg/dl. Sensitivity analyses were conducted to exclude factors such as potential confounders (including body mass index), misclassification of glycaemic level, and selection bias, and results showed that those factors could not explain the lower risk of active TB.

Conclusions

Prediabetes was associated with a 27% reduced risk of active TB disease compared with normoglycaemia. The biological mechanism of this inverse association and its implication for global nutrition transition and TB control should be further investigated.
The observable properties of cool winds from galaxies, AGN, and star clusters – II. 3D models for the multiphase wind of M82
Authors: Yuan Yuxuan , Krumholz Mark R , Martin Crystal L
Published: November 2022

Galactic winds are a crucial player in galaxy formation and evolution, but observations of them have proven extraordinarily difficult to interpret, leaving large uncertainties even in basic quantities such as mass outflow rates. Here we present an analysis of the wind of the nearby dwarf starburst galaxy M82 using a semi-analytic model that is able to take advantage of the full three-dimensional information present in position–position–velocity data cubes measured in the H i 21-cm line, the CO J = 2 → 1 line, and the Hα line. Our best-fitting model produces position-dependent spectra in good agreement with the observations, and shows that the total wind mass flux in the atomic and molecular phases is ≈10 M⊙ yr−1 (corresponding to a mass loading factor of ≈2–3), with less than a factor of 2 uncertainty; the mass flux in the warm ionized phase is more poorly constrained, and may be comparable to or smaller than this. At least over the few kpc off the plane for which we trace the outflow, it appears to be a wind escaping the galaxy, rather than a fountain that falls back. Our fits require that clouds of cool gas entrained into the wind expand only modestly, suggesting they are confined by magnetic fields, radiative cooling, or a combination of both. Finally, we demonstrate that attempts to model the wind using simplifying assumptions such as instantaneous acceleration and a constant terminal wind speed can yield significantly erroneous results.
Keck spectroscopy of the coma cluster ultra-diffuse galaxy Y358: dynamical mass in a wider context
Authors: Gannon Jonah S , Forbes Duncan A , Brodie Jean P , Romanowsky Aaron J , Couch Warrick J , Ferré-Mateu Anna
Published: November 2022

We examine ultra-diffuse galaxies (UDGs) and their relation to non-UDGs in mass–radius–luminosity space. We begin by publishing Keck/KCWI spectroscopy for the Coma cluster UDG Y358, for which we measure both a recessional velocity and velocity dispersion. Our recessional velocity confirms association with the Coma cluster and Y358’s status as a UDG. From our velocity dispersion (19 ± 3 km s−1), we calculate a dynamical mass within the half-light radius, which provides evidence for a core in Y358’s dark matter halo. We compare this dynamical mass, along with those for globular cluster (GC)-rich/-poor UDGs in the literature, to mass profiles for isolated, gas-rich UDGs, and UDGs in the NIHAO/FIRE simulations. We find GC-poor UDGs have dynamical masses similar to isolated, gas-rich UDGs, suggesting an evolutionary pathway may exist between the two. Conversely, GC-rich UDGs have dynamical masses too massive to be easily explained as the evolution of the isolated, gas-rich UDGs. The simulated UDGs match the dynamical masses of the GC-rich UDGs. However, once compared in stellar mass–halo mass space, the FIRE/NIHAO-simulated UDGs do not match the halo masses of either the isolated, gas-rich UDGs or the GC-rich UDGs at the same stellar mass. Finally, we supplement our data for Y358 with other UDGs that have measured velocity dispersions in the literature. We compare this sample to a wide range of non-UDGs in mass–radius–luminosity space, finding UDGs have a similar locus to non-UDGs of similar luminosity with the primary difference being their larger half-light radii.
Secular light curves of comets 60P/Tsuchinshan 2 and 62P/Tsuchinshan 1
Authors: Li Juncen , Shi Jianchun , Ma Yuehua
Published: November 2022

The activity of Jupiter family comets, 60P/Tsuchinshan 2 and 62P/Tsuchinshan 1, is analysed by creating their Secular light curves (SLCs). We collected 850 observations in apparitions 1995, 2005, 2012, and 2018 for 60P/Tsuchinshan 2 and 471 observations in apparitions 1998, 2004, and 2017 for 62P/Tsuchinshan 1. We obtained the main activity parameters: turn-on distance (RON) and time (TON), turn-off distance (ROFF) and time (TOFF), photometric age (P-AGE), and time age (T-AGE). The results show that both comets could be classified as middle-age comets in early apparitions, due to P-AGE ≳30 comet yr, and their activity lasting for more than 300 d similar to those of comets 32P/Comas-Sola and 67P/Churyumov–Gerasimenko. The orbital changes (decrease of perihelion distance) of comets 60P/Tsuchinshan 2 and 62P/Tsuchinshan 1 in recent apparitions enhanced their activity with different characteristics, which was proved by the increased brightness amplitude or space range of activity and the decreased P-AGE; meanwhile, they are entering the range of young comets, and are classified as Lazarus comets.
Selective degradation of tRNASer(AGY) is the primary driver for mitochondrial seryl-tRNA synthetase-related disease
Authors: Yu Tingting , Zhang Yi , Zheng Wen-Qiang , Wu Siqi , Li Guoqiang , Zhang Yong , Li Niu , Yao Ruen , Fang Pengfei , Wang Jian , Zhou Xiao-Long
Published: November 2022

Mitochondrial translation is of high significance for cellular energy homeostasis. Aminoacyl-tRNA synthetases (aaRSs) are crucial translational components. Mitochondrial aaRS variants cause various human diseases. However, the pathogenesis of the vast majority of these diseases remains unknown. Here, we identified two novel SARS2 (encoding mitochondrial seryl-tRNA synthetase) variants that cause a multisystem disorder. c.654–14T > A mutation induced mRNA mis-splicing, generating a peptide insertion in the active site; c.1519dupC swapped a critical tRNA-binding motif in the C-terminus due to stop codon readthrough. Both mutants exhibited severely diminished tRNA binding and aminoacylation capacities. A marked reduction in mitochondrial tRNASer(AGY) was observed due to RNA degradation in patient-derived induced pluripotent stem cells (iPSCs), causing impaired translation and comprehensive mitochondrial function deficiencies. These impairments were efficiently rescued by wild-type SARS2 overexpression. Either mutation caused early embryonic fatality in mice. Heterozygous mice displayed reduced muscle tissue-specific levels of tRNASers. Our findings elucidated the biochemical and cellular consequences of impaired translation mediated by SARS2, suggesting that reduced abundance of tRNASer(AGY) is a key determinant for development of SARS2-related diseases.
rG4detector, a novel RNA G-quadruplex predictor, uncovers their impact on stress granule formation
Authors: Turner Maor , Danino Yehuda M , Barshai Mira , Yacovzada Nancy S , Cohen Yahel , Olender Tsviya , Rotkopf Ron , Monchaud David , Hornstein Eran , Orenstein Yaron
Published: November 2022

RNA G-quadruplexes (rG4s) are RNA secondary structures, which are formed by guanine-rich sequences and have important cellular functions. Existing computational tools for rG4 prediction rely on specific sequence features and/or were trained on small datasets, without considering rG4 stability information, and are therefore sub-optimal. Here, we developed rG4detector, a convolutional neural network to identify potential rG4s in transcriptomics data. rG4detector outperforms existing methods in both predicting rG4 stability and in detecting rG4-forming sequences. To demonstrate the biological-relevance of rG4detector, we employed it to study RNAs that are bound by the RNA-binding protein G3BP1. G3BP1 is central to the induction of stress granules (SGs), which are cytoplasmic biomolecular condensates that form in response to a variety of cellular stresses. Unexpectedly, rG4detector revealed a dynamic enrichment of rG4s bound by G3BP1 in response to cellular stress. In addition, we experimentally characterized G3BP1 cross-talk with rG4s, demonstrating that G3BP1 is a bona fide rG4-binding protein and that endogenous rG4s are enriched within SGs. Furthermore, we found that reduced rG4 availability impairs SG formation. Hence, we conclude that rG4s play a direct role in SG biology via their interactions with RNA-binding proteins and that rG4detector is a novel useful tool for rG4 transcriptomics data analyses.