bluuebunny/crossref_metadata_2025 huggingface dataset:
Microraft arrays for serial‐killer CD19 chimeric antigen receptor T cells and single cell isolation
Authors: LaBelle Cody A. , Zhang Raymond J. , Hunsucker Sally A. , Armistead Paul M. , Allbritton Nancy L.
Published: July 2022

Chimeric antigen receptor T (CAR‐T) cell immunotherapies have seen success in treating hematological malignancies in recent years; however, the results can be highly variable. Single cell heterogeneity plays a key role in the variable efficacy of CAR‐T cell treatments yet is largely unexplored. A major challenge is to understand the killing behavior and phenotype of individual CAR‐T cells, which are able to serially kill targets. Thus, a platform capable of measuring time‐dependent CAR‐T cell mediated killing and then isolating single cells for downstream assays would be invaluable in characterizing CAR‐T cells. An automated microraft array platform was designed to track CD19 CAR‐T cell killing of CD19+ target cells and CAR‐T cell motility over time followed by CAR‐T cell collection based on killing behavior. The platform demonstrated automated CAR‐T cell counting with up to 98% specificity and 96% sensitivity, and single cells were isolated with 89% efficiency. On average, 2.3% of single CAR‐T cells were shown to participate in serial‐killing of target cells, killing a maximum of three target cells in a 6 h period. The cytotoxicity and motility of >7000 individual CAR‐T cells was tracked across four microraft arrays. The automated microraft array platform measured temporal cell‐mediated cytotoxicity, CAR‐T cell motility, CAR‐T cell death, and CAR‐T cell to target cell distances, followed by the capability to sort any desired CAR‐T cell. The pipeline has the potential to further our understanding of T cell‐based cancer immunotherapies and improve cell‐therapy products for better patient outcomes.
Chew's first Delaunay triangulation refinement scheme‐based positioning of road side units for optimal network coverage in vehicular ad‐hoc networks
Authors: Selvakumari PrabathKumar , Lakshmi Sree Rathna , Sheela Divakaran , Chinnasamy Ambayiram
Published: July 2022

The temporal network fragmentation and uncertain vehicle mobility are considered to impact the communication connectivity among the vehicular nodes of the network. In this context, road side units (RSUs) play an anchor role in enhancing the vehicle‐to‐vehicle (V2V) communication connectivity and support vehicle‐to‐infrastructure (V2I) communication. In the current scenario, deploying a huge number of RSUs in the vehicular networks at an initial stage is completely impossible as it incurs high installation cost and authority restriction. Moreover, the optimal placement of RSUs in the vehicular network needs to be enforced for attaining maximized network coverage. In this paper, Chew's first Delaunay triangulation refinement scheme (CFDTRS) is proposed for optimal positioning of RSUs in order to attain optimal network coverage in the vehicular network with minimized cost. This CFDTRS considered the factors of vehicular density, number of obstacles in the map, intersection popularity, and global coverage into account during the placement of RSUs. It is proposed with the objective of deploying required number of RSUs within the range of data transmission in order to achieve maximal coverage in the convex map, such that each area of the convex map is completely covered with at least a single RSU in the existence of multiple number of obstacles. The simulation results of the proposed CFDTRS attained from the real time situations of simplex, moderate, and complex maps confirmed improved packet delivery rate of 9.32%, throughput by 10.74% with minimized packet loss of 9.14%, and reduced end‐to‐end delay of 19.31$, compared to the benchmarked schemes considered for investigation.
Stabilization of fluvial bed sediments by invasive quagga mussels (Dreissena bugensis)
Authors: Sanders Harry , Mason Richard J. , Mills Daniel N. , Rice Stephen P.
Published: July 2022

River gravel mobility is an important control on river behaviour, morphology, and ecosystem processes. Gravel stability is dependent on abiotic flow and sediment properties, alongside less widely acknowledged biotic processes. The quagga mussel (Dreissena bugensis), a highly invasive bivalve, frequently occurs at high population densities in rivers and lakes. Quagga mussels attach to benthic sediments using byssal threads, which might affect sediment stability and thereby broader river geomorphology. We aimed to (1) characterize controls of quagga mussel sediment attachment by conducting a field survey in an invaded river, (2) investigate resultant changes in the critical shear stress needed to entrain fluvial bed materials via an ex situ flume experiment, for measured average (135 m−2) and potential future (270 m−2) mussel densities, and (3) model how this may affect sediment transport rates. From field surveys, mean quagga mussel density was 122 m−2, attaching to an average of 591 g m−2 of mineral bed sediments. Across the survey reach, mussels attached to all grain sizes available, with attachment driven by grain availability, rather than active selection of particular grain sizes. In the ex situ flume experiment, densities of 135 mussels m−2 did not significantly increase the critical shear stress of fluvial bed materials, but a density of 270 mussels m−2 significantly increased critical shear stress by 40%. Estimates of the proportion of time these critical stresses are exceeded at the field site indicated high densities of quagga mussels may reduce the occurrence of a geomorphically active flood event from Q30 to Q2. These results present feasible invasion scenarios, as quagga mussels frequently reach benthic densities orders of magnitude greater than observed here. This study indicates that substantial alterations to bedload sediment transport may occur following quagga mussel invasion. Future geomorphic modelling should include biology to better understand rates and processes of landscape development.
Perfluorononanoate and Perfluorobutane Sulfonate Induce Cardiotoxic Effects in Zebrafish
Authors: Gong Hongjian , Du Juan , Xu Jia , Yang Yuan , Lu Hui , Xiao Han
Published: July 2022

Globally, per- and polyfluoroalkyl substances are common artificial ingredients in industrial and consumer products. Recently, they have been shown to be an emerging human health risk. Perfluorononanoic acid (PFNA)/perfluorononanoate and perfluorobutane sulfonic acid (PFBS)/perfluorobutane sulfonate cause reproductive toxicity and hepatotoxicity, disrupt thyroid functions, and damage embryonic development in zebrafish. However, the cardiotoxic effects of PFNA and PFBS have not been fully established. We found that PFNA and PFBS exposures repress hatchability while increasing malformation and mortality in zebrafish embryos. Hematoxylin and eosin staining as well as assessment of the transgenic zebrafish line Tg(myl7:nDsRed) revealed that exposure of embryos to PFNA increases the occurrence of severe cardiac malformations relative to exposure to PFBS. Moreover, we evaluated the differential expressions of cardiac development-associated genes in response to PFNA and PFBS, which validated the potential cardiotoxic effects, consistent with cardiac dysfunctions. Overall, our findings reveal novel cardiotoxic effects of PFNA and PFBS in zebrafish, implying that they may exert some cardiotoxic effect in humans. To the best of our knowledge, ours is the first study to show that PFNA exerts more severe cardiotoxic effects in zebrafish when compared with PFBS. Based on these findings, studies should evaluate the mechanisms of their cardiotoxic effects. Environ Toxicol Chem 2022;41:2527–2536. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
Forecasting energy prices: Quantile‐based risk models
Authors: Apergis Nicholas
Published: July 2022

The goal of this paper is to use a new modelling approach to extract quantile‐based oil and natural gas risk measures using quantile autoregressive distributed lag mixed‐frequency data sampling (QADL‐MIDAS) regression models. The analysis compares this model to a standard quantile auto‐regression (QAR) model and shows that it delivers better quantile forecasts at the majority of forecasting horizons. The analysis also uses the QADL‐MIDAS model to construct oil and natural gas prices risk measures proxying for uncertainty, third‐moment dynamics, and the risk of extreme energy realizations. The results document that these risk measures are linked to the future evolution of energy prices, while they are linked to the future evolution of US economic growth.
Volatility forecasting for stock market incorporating macroeconomic variables based on GARCH‐MIDAS and deep learning models
Authors: Song Yuping , Tang Xiaolong , Wang Hemin , Ma Zhiren
Published: July 2022

Empirical experiments have shown that macroeconomic variables can affect the volatility of stock market. However, the frequencies of macroeconomic variables are low and different from the stock market volatility, and few literature considers the low‐frequency macroeconomic variables as input indicators for deep learning models. In this paper, we forecast the stock market volatility incorporating low‐frequency macroeconomic variables based on a hybrid model integrating the deep learning method with generalized autoregressive conditional heteroskedasticity and mixed data sampling (GARCH‐MIDAS) model to process the mixing frequency data. This paper firstly takes macroeconomic variables as exogenous variables then uses the GARCH‐MIDAS model to deal with the problem of different frequencies between the macroeconomic variables and stock market volatility and to forecast the short‐term volatility and finally takes the predicted short‐term volatility as the input indicator into machine learning and deep learning models to forecast the realized volatility of stock market. It is found that adding macroeconomic variables can significantly improve the forecasting ability in the comparison of the forecasting effects of the same model before and after adding the macroeconomic variables. Additionally, in the comparison of the forecasting effects among different models, it is also found that the forecasting effect of the deep learning model is the best, the machine learning model is worse, and the traditional econometric model is the worst.
Geochemistry of the Permian–Triassic boundary strata in the southwest margin of the North China Craton: Provenance and tectonic implications
Authors: Guo Bianqing , Gao Di , Guo Huiling , Liu Jianguo , Wang Jiahui , Shi Yi
Published: July 2022

The Late Permian Sunjiagou Formation and Early Triassic Liujiagou Formation were studied to understand the palaeoclimatic and palaeoenvironmental changes in the southwest margin of the North China Craton across the Permian–Triassic boundary, as well as the tectonic evolution of their provenance sediment. Major, trace, and rare earth elements in 20 clastic rock samples from the strata above and below the boundary were analysed. Overall, the Sunjiagou Formation samples showed an average index of compositional variability (ICV) and chemical index of alteration (CIA) of 1.53 and 73.59, respectively, indicating high‐maturity sediments in a warm and humid environment with moderate chemical weathering, whereas Liujiagou Formation samples had an average ICV and CIA of 2.40 and 70.1, respectively, indicating low‐maturity sediments in a cold and dry environment with mild chemical weathering. These strata were composed of first‐cycle sediments in a tectonically active area. The provenance of the Sunjiagou Formation was dominated by quartz‐rich sedimentary rocks, whereas that of Liujiagou Formation had both quartz‐rich sedimentary rocks and intermediate volcanic rocks. The provenance tectonic settings were mainly the continental island arc and active continental margin. Thus, the study area was in a terrestrial, freshwater sedimentary environment from the Late Permian to Early Triassic, and the climate gradually changed from warm and humid to dry and hot, with multiple small‐scale periodic evolutions. Taken together, these findings further confirm that the entire study area was in an oxidizing environment and the oxidation degree in the Early Triassic was higher than that in the Late Permian.
Surgical intervention after medical treatment for early pregnancy loss according to gestational size
Authors: Gluck Ohad , Barber Elad , Tal Ori , Kerner Ram , Weiner Eran , Sagiv Ron
Published: July 2022

Objective

To study the rate of surgical intervention for unsuccessful medical treatment in early pregnancy loss (EPL), according to gestational size by ultrasound (GS‐US).

Methods

This was a retrospective cohort study. All women who were treated with misoprostol for EPL between July 2015 and December 2020 were included. The cohort was divided according to GS‐US: group 1: gestational sac without an embryonic pole; group 2: an embryonic pole with crown‐rump length (CRL) compatible with <7 weeks; group 3: CRL compatible with 7+0–7+6 weeks; group 4: CRL compatible with 8+0–8+6 weeks; group 5: CRL compatible with ≥9 weeks. We compared the rate of any surgical intervention due to treatment failure.

Results

Overall, 783 patients were included: group 1, 236 (30.1%); group 2, 319 (40.7%); group 3, 115 (14.7%); group 4, 78 (10.0%); and group 5, 35 (5.0%) patients. The rate of any surgical intervention was significantly lower in groups 1–4 (54, 22.9%; 85, 26.6%; 28, 24.3%; and 22, 28.2%, respectively) compared with group 5 (17, 48.6%; P = 0.030). On multivariant analysis, GS‐US greater than 9 weeks was independently associated with the need for surgical intervention (adjusted odds ratio 1.23, 95% confidence interval 1.01–1.51; P = 0.040).

Conclusion

When treating EPL medically, GS‐US greater than 9 weeks increases the risk of undergoing additional surgical intervention compared with younger weeks.
Effect of intimate partner violence in pregnancy on maternal and perinatal outcomes at the Korle Bu teaching hospital, Ghana: An observational cross sectional study
Authors: Thompson Ngozi N. , Mumuni Kareem , Oppong Samuel A. , Sefogah Promise E. , Nuamah Mercy A. , Nkyekyer Kobinah
Published: July 2022

Objective

To determine the association between intimate partner violence and pregnancy outcomes.

Methods

This was a descriptive study of sociodemographic characteristics of participants, their partners and intimate partner violence. Participants' delivery records were reviewed for additional medical and obstetric information and abused women and their neonates followed until discharge. χ2 and Student t test were used to assess associations, followed by logistic regression with odds ratio (OR) and 95% confidence intervals (CI). A value of P less than 0.05 was considered statistically significant.

Results

The study included 270 participants of whom 84 (31.1%) reported experiencing domestic violence during pregnancy. One hundred and fourteen (42%) had experienced domestic violence pre‐pregnancy and 69 (60.5%) of these women experienced further domestic violence during pregnancy. Emotional violence was commonest 80/270 (29.6%) and no sexual violence was reported. Domestic violence declined from 42% (pre‐pregnancy) to 31.1% (in‐pregnancy) (P = 0.009). Risk factors during pregnancy were young age (15–24 years; OR 5.8, 95% CI1.65–20.38), nulliparity (OR 3.75, 95% CI 1.90–7.41), and partner's alcohol consumption (OR 5.04, 95% CI 2.50–10.13). Associated outcomes included late prenatal booking, gestational hypertension, and cephalopelvic disproportion.

Conclusion

We found high prevalence of domestic violence during pregnancy, preponderance of emotional abuse, and decline of physical abuse. Nulliparity, younger age, and partner's alcohol consumption predicted abuse. Late‐booking, gestational hypertension, cephalopelvic disproportion, and fetal distress were associated.
A simple guide to ultrasound screening for placenta accreta spectrum for improving detection and optimizing management in resource limited settings
Authors: Adu‐Bredu Theophilus K. , Rijken Marcus J. , Nieto‐Calvache Albaro Jose , Stefanovic Vedran , Aryananda Rozi Aditya , Fox Karin Anneliese , Collins Sally L. ,   the International Society of Placenta Accreta SPECTRUM (IS‐PAS) Low‐ and Middle‐Income Countries Working Group
Published: July 2022

Placenta accreta spectrum is a pregnancy complication associated with severe morbidity and maternal mortality especially when not suspected antenatally and appropriate management instigated. Women in resource‐limited settings are more likely to face adverse outcomes due to logistic, technical, and resource inadequacies. Accurate prenatal imaging is an important step in ensuring good outcomes because it allows adequate preparation and an appropriate management approach. This article provides a simple three‐step approach aimed at guiding clinicians and sonographers with minimal experience in placental accreta spectrum through risk stratification and basic prenatal screening for this condition both with and without Doppler ultrasound.
Capacity building in operational research on obstetric fistula: Experience in the Democratic Republic of Congo, 2017–2021
Authors: Delamou Alexandre , Tripathi Vandana , Camara Bienvenu Salim , Sidibe Sidikiba , Grovogui Fassou Mathias , Kolie Delphin , Bouedouno Patrice , Kourouma Karifa , Banze Don Félicien , Mafu Michel M.
Published: July 2022

Objective

To implement a Flexible Operational Research Training (FORT) course within the Fistula Care Plus Project, Democratic Republic of Congo, from 2017 to 2021.

Methods

A descriptive study using design and implementation (process and outcome) data. Two to four members of medical teams from three supported sites were selected for the training based on their research interests and level of involvement in the program.

Results

Two courses (13–14 months each) involving nine facilitators and 17 participants overall were conducted between 2017 and 2021. Most participants in both courses were medical doctors (67% and 71%, respectively) from the supported hospitals (83% and 77%, respectively). About half were women. In addition to classic face‐to‐face didactic modules, the courses integrated online platforms to cope with the changing contexts (Ebola virus and COVID‐19). Most participants reported having gained new skills in developing research protocols, collecting, managing, and analyzing data, and developing research manuscripts. The two courses resulted in six scientific manuscripts and three presentations at international conferences. Participants subsequently published five papers from their research after the first course. The total direct costs for both courses were representing a cost of $3669 per participant trained.

Conclusion

The FORT model proved feasible, efficient, and successful. However, scaling up will require more adaptation efforts from programs and participating sites.
Determination of groundwater potential zones using geographic information systems and remote sensing in Lupane District, Zimbabwe
Authors: Chisadza Bright , Mashakani Brian‐Lee , Gwate Onalenna , Chiwara Phibion , Choruma Dennis , Gumindoga Webster
Published: July 2022

Groundwater is a vital natural resource for agricultural, domestic and industrial uses. Understanding the spatial distribution of groundwater resources is critical to improving the relationship between water, food and energy. This article uses GIS and remote sensing and the analytical hierarchy process (AHP) technique to map the potential groundwater zones in the Lupane district. Lineaments, drainage density, slope, soil type, geology and land use land cover (LULC) were used to create thematic maps in ArcMap. The thematic maps were weighted and ranked according to their influence on the movement and occurrence of groundwater. To validate the groundwater potential zones (GWPZs) model, we used LULC and 675 perennial and seasonal boreholes in the Lupane district. The LULC and borehole maps were overlaid on the modelled GWPZ map to highlight their distribution. The GWPZ results show that areas with good potential make up the majority of the district (41%), followed by areas with moderate potential (30%), poor potential (14%), very good potential (13%) and very poor potential (2%). The results showed that 74% (499) of perennial boreholes overlapped the zones with good, moderate and/or very good groundwater potential. The GWPZ map can therefore be used as a preliminary reference when selecting suitable sites for the exploitation of groundwater resources. Further testing of the model using both seasonal and year‐round yields and depths from boreholes is recommended.
NTBI levels in C282Y homozygotes after therapeutic phlebotomy
Authors: Ryan Eleanor , Mulready Keith , Wiegerinck Erwin , Russell Jennifer , Swinkels Dorine W. , Stewart Stephen
Published: July 2022

C282Y homozygotes exposed to sustained elevated transferrin saturation (TS) may develop worsening clinical symptoms. This might be related to the appearance of non‐transferrin bound iron (NTBI) when TS≥50% and labile plasma iron (LPI) when TS levels reach 75–80%. In this study, NTBI levels were examined in 219 randomly selected untreated and treated C282Y homozygotes. Overall, 161 of 219 had TS ≥ 50%, 124 of whom had detectable NTBI (≥0.47 µM, 1.81 µM [0.92–2.46 µM]) with a median serum ferritin 320 µg/L (226–442 µg/L). Ninety of 219 homozygotes had TS ≥ 75%, and all had detectable NTBI (2.21 µM [1.53–2.59 µM] with a median ferritin 338 µg/L [230–447 µg/L]). Of 125 homozygotes who last had phlebotomy ≥12 months ago (42 months [25–74 months], 92 had TS levels ≥ 50%, and 70 of these had NTBI ≥ 0.47 µM (2.06 µM [1.23–2.61µM]). Twenty‐six of these 70 had a normal ferritin. Fifty‐five of 125 had TS ≥ 75%, and NTBI was detected in all of these (2.32 µM [1.57–2.77 µM]) with a median ferritin 344 µg/L (255–418 µg/L). Eighteen of these 55 had a normal ferritin. In summary, NTBI is frequently found in C282Y homozygotes with TS ≥ 50%. Furthermore, C282Y homozygotes in the maintenance phase often have TS ≥ 50% together with a normal ferritin. Therefore, monitoring the TS level during the maintenance phase is recommended as an accessible clinical marker of the presence of NTBI.
Pharmacologic screen identifies active combinations with BET inhibitors and LRRK2 as a novel putative target in lymphoma
Authors: Spriano Filippo , Sartori Giulio , Tarantelli Chiara , Barreca Marilia , Golino Gaetanina , Rinaldi Andrea , Napoli Sara , Mascia Michele , Scalise Lorenzo , Arribas Alberto J. , Cascione Luciano , Zucca Emanuele , Stathis Anastasios , Gaudio Eugenio , Bertoni Francesco
Published: July 2022

Inhibitors of the Bromo‐ and Extra‐Terminal domain (BET) family proteins have strong preclinical antitumor activity in multiple tumor models, including lymphomas. Limited single‐agent activity has been reported in the clinical setting. Here, we have performed a pharmacological screening to identify compounds that can increase the antitumor activity of BET inhibitors in lymphomas.

The germinal center B‐cell like diffuse large B‐cell lymphoma (DLBCL) cell lines OCI‐LY‐19 and WSU‐DLCL2 were exposed to 348 compounds given as single agents at two different concentrations and in combination with the BET inhibitor birabresib. The combination partners included small molecules targeting important biologic pathways such as PI3K/AKT/MAPK signaling and apoptosis, approved anticancer agents, kinase inhibitors, epigenetic compounds. The screening identified a series of compounds leading to a stronger antiproliferative activity when given in combination than as single agents: the histone deacetylase (HDAC) inhibitors panobinostat and dacinostat, the mTOR (mechanistic target of rapamycin) inhibitor everolimus, the ABL/SRC (ABL proto‐oncogene/SRC proto oncogene) inhibitor dasatinib, the AKT1/2/3 inhibitor MK‐2206, the JAK2 inhibitor TG101209. The novel finding was the benefit given by the addition of the LRRK2 inhibitor LRRK2‐IN‐1, which was validated in vitro and in vivo. Genetic silencing demonstrated that LRRK2 sustains the proliferation of lymphoma cells, a finding paired with the association between high expression levels and inferior outcome in DLBCL patients.

We identified combinations that can improve the response to BET inhibitors in lymphomas, and LRRK2 as a gene essential for lymphomas and as putative novel target for this type of tumors.
Pediatric inborn errors of immunity causing hemophagocytic lymphohistiocytosis: Case report and review of the literature
Authors: Caldirola María Soledad , Raccio Andrea Gómez , Di Giovanni Daniela , Gaillard María Isabel , Preciado María Victoria
Published: July 2022

Inborn errors of immunity are a group of genetic disorders caused by mutations that affect the development and/or function of several compartments of the immune system, predisposing patients to infections, autoimmunity, allergy and malignancies. In this regard, mutations that affect proteins involved in trafficking, priming, docking, or membrane fusion will impair the exocytosis of lytic granules of effector NK and cytotoxic T lymphocytes. This may predispose patients to hemophagocytic lymphohistiocytosis, a life-threatening immune disorder characterized by systemic lymphocyte and macrophage activation, and increased levels of cytokines, which lead to an uncontrolled hyperinflammation state and progressive multiorgan damage. In this review, we will describe a clinical case and recent advances in inborn errors of immunity predisposing to hemophagocytic lymphohistiocytosis.

Summary sentence: Review of recent advances in inborn errors of immunity predisposing to hemophagocytic lymphohistiocytosis.
Primary carnitine deficiency is a life‐long disease
Authors: Crefcoeur Loek L. , Melles Mireille C. , Bruning Tobias A. , Pereira Rob Rodrigues , Langendonk Janneke G.
Published: July 2022

Primary carnitine deficiency is a rare autosomal recessive disease associated with acute hypoketotic hypoglycaemia, cardiomyopathy and sudden cardiac death. Effective treatment with carnitine supplementation is available. An 18 months old boy, who presented with cardiomyopathy was diagnosed with primary carnitine deficiency, and carnitine supplementation resulted in a full recovery. At age 13 years, he discontinued his medication and at 20 years, he discontinued clinical monitoring. Nine years later, age 29, he presented with heart failure and atrial fibrillation and was admitted to an intensive care unit, where he was treated with furosemide, enoximone and intravenous carnitine supplementation, this lead to improved cardiac function within 2 weeks, and with continued oral carnitine supplements, his left ventricular ejection fraction normalised. The last 8 years were uneventful and he continued to attend his regular follow‐up visits at a specialised metabolic outpatient clinic. We report recurrent reversible severe heart failure in a patient with primary carnitine deficiency; it was directly related to non‐compliance to carnitine supplementation (and monitoring). This case report emphasises first, the importance of continued monitoring of metabolic disease patients, second, the potential reversibility of cardiomyopathy in an adult patient, and third, the potential risks in the period of transition from the paediatric to adult care. This is an age where young adults desire to be healthy and ignore the need for ongoing medical treatment, even as simple as oral suppletion. Before they reach this age, adequate disease insight and self‐management of the disease should be promoted.
Association of type II diabetes mellitus with characteristics and outcomes for patients undergoing sentinel lymph node biopsy for cutaneous melanoma
Authors: Straker Richard J. , Tortorello Gabriella N. , Sharon Cimarron E. , Keele Luke J. , Chu Emily Y. , Miura John T. , Karakousis Giorgos C. , Ming Michael E.
Published: July 2022

Background and Objectives

Type II diabetes mellitus (T2DM) can lead to an immunosuppressed state, but whether T2DM is associated with worse outcomes for patients with melanoma has not been well studied.

Methods

Consecutive patients diagnosed with clinical stage I–II cutaneous melanoma who underwent sentinel lymph node biopsy at a single institution (2007–2016) were identified. Melanoma characteristics and recurrence/survival outcomes were compared between patients with and without T2DM at the time of melanoma diagnosis.

Results

Of 1128 patients evaluated, 111 (9.8%) had T2DM (n = 94 [84.7%] non‐insulin dependent [NID‐T2DM]; n = 17 [15.3%] insulin dependent [ID‐T2DM]). T2DM patients were more likely to be older (odds ratio [OR] 1.04, p < 0.001), male (OR 2.15, p = 0.003), have tumors >1.0 mm (OR 1.88, p = 0.023), and have microsatellitosis (OR 2.29, p = 0.030). Five‐year cumulative incidence of melanoma recurrence was significantly higher for patients with ID‐T2DM (46.7% ID‐T2DM vs. 25.7% NID‐T2DM vs. 17.1% no T2DM, p < 0.001), and on multivariable analysis, ID‐T2DM was independently associated with melanoma recurrence (hazard ratio 2.57, p = 0.015). No difference in 5‐year disease‐specific survival was observed between groups.

Conclusions

ID‐T2DM appears to be associated with more advanced melanoma and increased risk for melanoma recurrence. Further study as to whether this reflects differences in tumor biology or host factors is warranted.
Lifetime trauma exposure profiles and alcohol use over time among U.S. Reserve and National Guard soldiers
Authors: Vest Bonnie M. , Weiss‐Laxer Nomi S. , Homish D. Lynn , Homish Gregory G.
Published: July 2022

Although trauma exposure is a recognized risk factor for alcohol use, research on military populations has emphasized combat exposure, with minimal consideration of exposure to other potentially traumatic events (PTEs). We aimed to (a) identify, characterize, and quantify subgroups of service members based on PTE patterns; (b) examine associations between trauma exposure subgroups and alcohol use; and (c) examine these associations longitudinally. Data were drawn from Operation: SAFETY, a longitudinal study of health and well‐being among U.S. Army Reserve/National Guard soldiers (N = 478). Exposure to 15 PTEs, including childhood maltreatment, noninterpersonal events (e.g., natural disasters, accidents), interpersonal trauma, and military‐related exposures, was assessed at baseline. Latent profile analysis was conducted to characterize mutually exclusive trauma profiles; profile membership was used to longitudinally predict alcohol use in generalized estimating equation models. Four exposure profiles were identified: intimate partner violence (IPV)/combat trauma (8.4%, n = 40), combat trauma (24.7%, n = 118), childhood trauma (8.4%, n = 40), and low trauma (58.6%, n = 280). In adjusted models, compared to the low trauma profile, IPV/combat profile membership was longitudinally associated with alcohol problems, OR = 2.44, p =.005. Membership in other trauma profiles was not associated with alcohol use. Within the IPV/combat profile, men had a higher risk of frequent heavy drinking than women. Results suggest a need to comprehensively screen for lifetime PTE exposure, particularly IPV, in military populations. Given the high prevalence of nonmilitary PTEs, an inclusive, trauma‐informed approach to health care and service provision is warranted.
Towards sustainable and efficient land development: Risk of soil heavy metal(loid)s in abandoned gold mines with short‐term rehabilitation and potential value for targeted remediation
Authors: Cao Lina , Xiang Hongyong , Yang Pan , Zhang Zhenxing , He Chunguang , Lin Chenlu , Gao Yufu , Li Yuan , Bernhardt Thibault M.
Published: July 2022

Recently sustainable and efficient land development and the potential reutilization values of abandoned mines (i.e., industrial, arable, and tourism) have been attracting worldwide attention. However, environmental impacts after rehabilitation practices are often ignored and field data are lacking. What remains unknown is an understanding how the risk of soil trace metal(loid)s (TMs) respond to short‐term rehabilitation of abandoned gold mines and the potential value for following targeted remediation. We found that a high level of TM cadmium (Cd) and arsenic (As)] contamination and significant health risk to humans, limited land reutilization in rehabilitation scenarios. Feedback from soil TMs to rehabilitation is of potential value for following targeted remediation. Specifically, (1) the major pollutants we studied were Cd and As. Cadmium poses a considerable ecological risk as evidenced by Igeo, contamination factor, and risk assessment code, and a much higher bioavailability evidenced by non‐residual fractions (42.42%). Arsenic has the lowest environmental availability with 90.99% in residual fraction; (2) spatial distributions of TMs were similar. Sites with serious contamination were mainly located in the southwest of the study area, close to the abandoned mine; Results of principal component analysis suggested that mining activities were the main anthropogenic pollution sources; (3) there was no non‐carcinogenic risk and a higher carcinogenic risk was found in adults than in children. Targeted remediation techniques are needed to mitigate carcinogenic risks posed by As and Cr. This study emphasized the necessity of assessment of soil TMs risk in abandoned gold mines with short‐term rehabilitation and offered crucial data utilized to optimize time parameters (short‐term) towards sustainable and efficient land development.
Hypoglossal nerve stimulator patient usage: Patterns and trends over time
Authors: Morse Elliot , Suurna Maria
Published: July 2022

Objective

Hypoglossal nerve stimulation (HNS) is an effective treatment for obstructive sleep apnea (OSA) patients intolerant of continuous positive airway pressure but is only effective if used regularly. Usage patterns have not been studied in detail. In this study, we aimed to characterize granular HNS usage patterns.

Methods

Patients implanted by a single surgeon at an academic medical center from August 2016 to January 2021 were identified from a prospective database, which was merged with the Inspire Cloud usage database. Patient, OSA, and usage characteristics were summarized, and patient‐ and OSA‐related characteristics were associated with usage characteristics by Wilcoxon rank‐sum analyses. Usage trends over time were summarized in the overall cohort and stratified by initial usage.

Results

Fifty patients were included. Median usage was 94% of nights (interquartile range [IQR]: 82%–98%) for 5.8 h per night (IQR: 4.9–6.4). Higher post‐operative apnea–hypopnea index predicted fewer nights used (92% [IQR: 82%–97%] vs. 96% [IQR: 91%–99%]). No other characteristics examined were significantly associated with usage. Median hours used per night decreased from 6.80 h (IQR: 5.32–7.94) on Day 1 to 5.76 (IQR: 1.81–7.13) on Day 361. This decrease was most pronounced in the quartile with the lowest initial usage.

Conclusion

This study found that most patient and OSA characteristics were not associated with HNS usage, and that usage generally decreased over time. This decrease in usage over time was most pronounced in patients with the lowest initial usage. Further work should identify interventions to improve usage patterns to optimize clinical outcomes.

Level of Evidence: 4.
Otolaryngology residents' experiences of pregnancy and return to work: A multisite qualitative study
Authors: Champaloux Eve P. , Acosta Anne Starks , Gray Stacey T. , Meyer Tanya K. , Bergmark Regan W.
Published: July 2022

Objectives

A paucity of literature exists about childbearing during otolaryngology residency. Pregnancy is a common part of many physician life cycles, but the timing of residency and the rigors of surgical training amplify the challenges. This study was designed to understand the experiences of childbearing otolaryngology residents and support them during this major life event. Unique challenges include long training, shortage of role models, combination surgical and clinical work, and higher rates of infertility.

Study Design

Qualitative research. IRB exempt.

Setting

United States.

Methods

To capture modern perspectives, 16 current and former otolaryngology residents that experienced pregnancy and childbirth during residency in all four geographic regions of the United States in the past 10 years were recruited to participate in individual structured qualitative interviews.

Results

Although there was significant training program and personal anxiety reported by childbearing otolaryngology residents, many surgeons experienced healthy pregnancies and postpartum recoveries with minimal disruption to clinical productivity and minimal disruption to their training programs. Multiple recurring themes were identified among the participants spanning the entire childbearing process: increased incidence of pregnancy complications and preterm labor, pregnancy stigma from leadership and coresidents, scheduling logistics regarding call and parental leave, and challenging transitions back to clinical work while navigating breastfeeding and childcare.

Conclusion

There are actional recommendations that programs can address to make childbearing during residency accessible and acceptable. Understanding these challenges is an important step to encouraging childbearing residents to prosper in academic otolaryngology, increasing the diversity at the highest levels of the field.

Level of Evidence

4.
Mass spectrometry in organic and bio‐organic catalysis: Using thermochemical properties to lend insight into mechanism
Authors: Hinz Damon J. , Zhang Lanxin , Lee Jeehiun K.
Published: July 2022

In this review, we discuss gas phase experimentation centered on the measurement of acidity and proton affinity of substrates that are useful for understanding catalytic mechanisms. The review is divided into two parts. The first covers examples of organocatalysis, while the second focuses on biological catalysis. The utility of gas phase acidity and basicity values for lending insight into mechanisms of catalysis is highlighted.
A rotational velocity‐correction projection method for the Kelvin–Voigt viscoelastic fluid equations
Authors: Si Zhiyong , Wang Qing , Wang Yunxia
Published: July 2022

In this paper, a semi‐discrete rotational velocity‐correction projection method is proposed to solve the Kelvin–Voigt viscoelastic fluid equations. In this method, the rotational velocity‐correction projection method can preserve the divergence free of the velocity
, and the nonlinear equation was linearized. Then, the unconditional stability and optimal convergence order will be provided by the numerical analysis. Finally, our analysis are confirmed by some numerical results, and the algorithm is effective.
Passively Q‐switched Tm:YAP laser with a Ti3AlC2‐based saturable absorber
Authors: Liu Bangzheng , Yang Wenlong , Gao Qiong , Yang Xining , Li Linjun , Shen Yingjie , Zong Tianhao , Cui Haoyu
Published: July 2022

In this paper, a passively Q‐switched (PQS) Tm:YAP laser was experimentally demonstrated by using a Ti3AlC2‐based saturable absorber (SA). In the PQS regime, an average output power of 2010/1575 mW with a pulse width of 266/859 ns at 130/155 kHz was achieved from a Tm:YAP laser under an output couple mirror with a transmittance (T) of 1.5%/2.5%, corresponding to an optical conversion efficiency of 9.2%/11.6%. Also, a single pulse energy of 15.5/10.2 μJ and a peak power of 58.1/11.8 W were acquired from the PQS Tm:YAP laser. As far as we know, this is the first time that a Ti3AlC2‐based SA was used for a PQS Tm:YAP laser.
Time domain NMR: An alternative for study of the asphaltenes precipitated in petroleum
Authors: Morgan Vinícius G. , Sad Cristina M. S. , Leite Juliete S. D. , Castro Eustáquio R. V. , Barbosa Lúcio L.
Published: July 2022

During the oil production and processing stages, the asphaltene precipitation is one of the great operation problems of oil industry. It can precipitate in the formation, tubing, or surface, causing operating problems, such as reduction in oil recovery by changing the reservoir permeability and wettability, clogging of the pipelines, and difficulty in separations process. The quantification of asphaltenes in petroleum by ASTM D6560 standard method is very laborious and use of a larger solvent volume than necessary. The present work proposes the use of time domain nuclear magnetic resonance (TD‐NMR) as new methodology to quantify the asphaltene precipitated in crude oil. Three (light, medium, and heavy) crude oils with asphaltenes content of 0.97, 1.88, and 7.00 wt% were mixed with n‐heptane in different R (ml of solvent/g of oil) values and analyzed by means of transverse relaxation time (T2). According NMR results, the R values enough for complete asphaltene precipitation for the oils A, B, and C were, respectively, equal to 16.50, 23.00, and 39.50 ml g−1. These outcomes represent a reduction of 58.75%, 42.50%, and 1.25% in the solvent volume per mass of oil for the oil A, B, and C, respectively, compared to the ASTM D6560 method, which imposes 40 ml g−1. Therefore, it has been shown that TD‐NMR can be applied to estimate the amount of asphaltene precipitated in petroleum and have potential to be applied in routine analysis with advantages of saving time and costs.
Prospective, multicenter study to evaluate performance and safety of a re‐engineered temporary lead for InterStim™ therapy evaluation
Authors: Elterman Dean , Michaels Jodi , Margolis Eric , Harris‐Hicks Janet , Burgess Kimberly , Betts Christopher , Harding Christopher , Towers Geoffrey , Hashim Hashim , Ojo‐Carons Akin , White Amanda , Cannon‐Smith Tracy , Grunow Nathan , Bittner Katie , Xavier Keith
Published: July 2022

Aims

The basic evaluation or percutaneous nerve evaluation (PNE) is a method to assess pre‐implantation therapeutic response in patients considering sacral neuromodulation for the treatment of refractory overactive bladder. A new PNE lead with a more robust design and greater distensibility designed to reduce the possibility of lead migration has recently been introduced to the market. The aim of this prospective, multicenter, global, postmarket study was to evaluate the clinical performance and safety of the new InterStim PNE lead with the foramen needle.

Methods

Patients with overactive bladder were enrolled in this study. The primary objective of this study was to determine the proportion of subjects who demonstrated motor or sensory response(s) during lead placement using the InterStim PNE lead. Additional measures included the Patient Global Impression of Improvement (PGI‐I), patient satisfaction at the end of therapy evaluation, and change in bladder symptoms from baseline to the end of therapy evaluation (1‐week follow‐up visit).

Results

One‐hundred and ten subjects met the inclusion and exclusion criteria and underwent a lead implant procedure. Of those, 108 had a successful procedure and 107 completed the 1‐week follow‐up visit. Ninety‐nine percent of subjects (109/110) had a motor or sensory response during needle placement (95% confidence interval [CI]: 95%–100%) and 97% of subjects (107/110) had a motor or sensory response during lead placement (95% CI: 92%–99%). The majority of subjects (88%, 95/108) reported their bladder condition was better at the follow‐up visit compared to before the PNE implant procedure, as reported in PGI‐I. Subjects reported being satisfied with how the therapy impacted their voiding symptoms (82%, 88/108) and that they would recommend this therapy (87%, 94/108) to other patients. Symptom improvement was demonstrated with urinary urge incontinence subjects having an average of 4.2 ± 3.4 urinary incontinence episodes/day at baseline and 2.2 ± 2.5 at follow‐up, and urinary frequency subjects having an average of 12.5 ± 4.4 voids/day at baseline and 10.5 ± 4.3 voids/day at follow‐up. Lead removal was deemed to be easy and safe by the implanting physician, with a total of three adverse device effects in 3/110 subjects. No event was categorized as serious and all were resolved without sequelae.

Conclusions

The updated InterStim PNE lead with a more robust design and greater distensibility designed to reduce migration was shown to have a high rate of motor or sensory response during lead placement. Furthermore, subjects reported high rates of global improvements and amelioration of symptoms, and the lead was easy to remove with minimal morbidity.
Numerical analysis and theoretical studies on the axial compression behavior of multi‐cell Al‐CFRP hybrid tubes
Authors: Qin Xiaoyu , Ma Qihua , Gan Xuehui , Bai Cuiping
Published: July 2022

To find a thin‐walled impact‐resistant structure with excellent crushing performance, a multi‐cell hybrid thin‐walled tube (MCHT) formed by winding carbon fibers around a multi‐cell Al tube was proposed. The structure is designed based on different structural parameters of the thin‐walled tubes exhibiting different crushing characteristics and damage modes. First, a finite element model applicable to MCHT is established, and the accuracy of the model is verified by quasi‐static axial pressure experiments. Second, the verified finite element model was used to study the variation law of the overall structural crushing performance by changing the structural parameters of MCHT, and the Al tube wall thickness was found to have the greatest effect on MCHT crushing performance, followed by the number of ribs and finally the inner circle diameter. Then, a theoretical prediction model of the mean crushing force of MCHT was established based on the principle of energy conservation, and the accuracy of the theoretical model was initially verified through experiments. Finally, to overcome the problem that the prediction error of the theoretical model is larger when the number of ribs is larger or the inner circle diameter is smaller, a correction function is constructed based on Pearson correlation coefficient analysis to further improve the generalization ability of the above‐mentioned theoretical model, and the maximum relative error is reduced from 37% to 14.61%.
Identification of 22q11.2 deletion in a patient with schizophrenia and clinically diagnosed Rubinstein–Taybi syndrome
Authors: Nagai Yasuhito , Nishioka Masaki , Tanaka Tatsuki , Shimano Takahisa , Kirino Eiji , Suzuki Toshihito , Kato Tadafumi
Published: July 2022

Background

Rubinstein–Taybi syndrome (RTS) is a rare autosomal‐dominant disease. Almost all cases are sporadic and attributed to de novo variant. Psychotic symptoms in RTS are rare and have been reported in only a few published cases. On the other hand, 22q11.2 deletion syndrome is the most common chromosomal microdeletion in humans. The 22q11.2 deletion is well recognized as a risk factor for schizophrenia. Here, we present a schizophrenic psychosis case clinically diagnosed as RTS but resolved as carrying 22q11.2 deletion by genomic analysis.

Case presentation

A 38‐year‐old Japanese male was admitted to our hospital due to psychotic symptoms. He had been diagnosed with RTS based on physical characteristics at the age of 9 months. On admission, we performed whole exome sequencing. He had no pathogenic variant in CREBBP or EP300. We detected 2.5 Mb deletion on 22q11.2 and one rare loss‐of‐function variant in a loss‐of‐function‐constrained gene (MTSS1) and three rare missense variants in missense‐constrained genes (CELSR3, HERC1, and TLN1). Psychotic symptoms were ameliorated by the treatment of risperidone.

Conclusion

The psychiatric manifestation and genomic analysis may be a clue to detecting 22q11.2 deletion syndrome in undiagnosed patients. The reason for similarity in physical characteristics in 22q11.2 deletion syndrome and RTS remains unresolved. The 22q11.2 deletion and HERC1 contribute to the patient's phenotype.