bluuebunny/crossref_metadata_2025 huggingface dataset:
Proteomic and functional analysis of HDL subclasses in humans and rats: a proof-of-concept study
Authors: Huang Canxia , Zhang Jie , Huang Jingjing , Li Hongwei , Wen Kexin , Bao Jinlan , Wu Xiaoying , Sun Runlu , Abudukeremu Ayiguli , Wang Yue , He Zhijian , Chen Qiaofei , Huang Xinyi , Wang Hong , Zhang Yuling
Published: June 2023

Background

The previous study investigated whether the functions of small, medium, and large high density lipoprotein (S/M/L-HDL) are correlated with protein changes in mice. Herein, the proteomic and functional analyses of high density lipoprotein (HDL) subclasses were performed in humans and rats.

Methods

After purifying S/M/L-HDL subclasses from healthy humans (n = 6) and rats (n = 3) using fast protein liquid chromatography (FPLC) with calcium silica hydrate (CSH) resin, the proteomic analysis by mass spectrometry was conducted, as well as the capacities of cholesterol efflux and antioxidation was measured.

Results

Of the 120 and 106 HDL proteins identified, 85 and 68 proteins were significantly changed in concentration among the S/M/L-HDL subclasses in humans and rats, respectively. Interestingly, it was found that the relatively abundant proteins in the small HDL (S-HDL) and large HDL (L-HDL) subclasses did not overlap, both in humans and in rats. Next, by searching for the biological functions of the relatively abundant proteins in the HDL subclasses via Gene Ontology, it was displayed that the relatively abundant proteins involved in lipid metabolism and antioxidation were enriched more in the medium HDL (M-HDL) subclass than in the S/L-HDL subclasses in humans, whereas in rats, the relatively abundant proteins associated with lipid metabolism and anti-oxidation were enriched in M/L-HDL and S/M-HDL, respectively. Finally, it was confirmed that M-HDL and L-HDL had the highest cholesterol efflux capacity among the three HDL subclasses in humans and rats, respectively; moreover, M-HDL exhibited higher antioxidative capacity than S-HDL in both humans and rats.

Conclusions

The S-HDL and L-HDL subclasses are likely to have different proteomic components during HDL maturation, and results from the proteomics-based comparison of the HDL subclasses may explain the associated differences in function.
Du Huo Ji Sheng Tang inhibits Notch1 signaling and subsequent NLRP3 activation to alleviate cartilage degradation in KOA mice
Authors: Chen Wen-jin , Zhuang Yin , Peng Wei , Cui Wei , Zhang Shu-jun , Wang Jian-wei
Published: June 2023

Background

Knee osteoarthritis (KOA) has a complex pathological mechanism and is difficult to cure. The traditional medicine Du Huo Ji Sheng Tang (DHJST) has been used for the treatment of KOA for more than one thousand years, but its mechanism for treating KOA has not been revealed. In our previous study, we confirmed that DHJST inhibited the activation of NLRP3 signaling in rats and humans. In the current study, we aimed to determine how DHJST inhibits NLRP3 to alleviate knee cartilage damage.

Methods

Mice were injected with NLRP3 shRNA or Notch1-overexpressing adenovirus into the tail vein to construct systemic NLRP3 low-expressing or Notch1 high-expressing mice. Mice were injected with papain into the knee joint to replicate the KOA model. DHJST was used to treat KOA model mice with different backgrounds. The thickness of the right paw was measured to evaluate toe swelling. The pathohistological changes and the levels of IL-1β, MMP2, NLRP3, Notch1, collagen 2, collagen 4, HES1, HEY1, and Caspase3 were detected by HE staining, ELISA, immunohistochemical staining, western blotting, or real-time qPCR.

Results

DHJST reduced tissue swelling and serum and knee cartilage IL-1β levels, inhibited cartilage MMP2 expression, increased collagen 2 and collagen 4 levels, decreased Notch1 and NLRP3 positive expression rates in cartilage, and decreased HES1 and HEY1 mRNA levels in KOA model mice. In addition, NLRP3 interference decreased cartilage MMP2 expression and increased collagen 2 and collagen 4 levels without affecting the expression levels of notch1, HES1 and HEY1 mRNA levels in the synovium of KOA mice. In KOA mice with NLRP interference, DHJST further reduced tissue swelling and knee cartilage damage in mice. Finally, Notch1-overexpressing mice not only showed more severe tissue swelling and knee cartilage degradation but also abolished the therapeutic effect of DHJST on KOA mice. Importantly, the inhibitory effects of DHJST on the mRNA expression of NLRP3, Caspase3 and IL-1β in the knee joint of KOA mice were completely limited after Notch1 overexpression.

Conclusion

DHJST significantly reduced inflammation and cartilage degradation in KOA mice by inhibiting Ntoch1 signaling and its subsequent NLRP3 activation in the knee joint.
Efficient and versatile multiplex prime editing in hexaploid wheat
Authors: Ni Pei , Zhao Yidi , Zhou Ximeng , Liu Zehua , Huang Zhengwei , Ni Zhongfu , Sun Qixin , Zong Yuan
Published: June 2023

Prime editing is limited by low efficiency in plants. Here, we develop an upgraded engineered plant prime editor in hexaploid wheat, ePPEplus, by introducing a V223A substitution into reverse transcriptase in the ePPEmax* architecture. ePPEplus enhances the efficiency by an average 33.0-fold and 6.4-fold compared to the original PPE and ePPE, respectively. Importantly, a robust multiplex prime editing platform is established for simultaneous editing of four to ten genes in protoplasts and up to eight genes in regenerated wheat plants at frequencies up to 74.5%, thus expanding the applicability of prime editors for stacking of multiple agronomic traits.
The triglyceride-glucose index as a potential protective factor for hypertrophic obstructive cardiomyopathy without diabetes: evidence from a two-center study
Authors: Meng Xiangbin , Gao Jun , Zhang Kuo , Jun Wen , Wang Jing-Jia , Wang Xu-Liang , Wang Yuan-Geng-Shuo , Zheng Ji-Lin , Liu Yu-Peng , Song Jing-Jing , Yang Jie , Zheng Yi-Tian , Li Chen , Wang Wen-Yao , Shao Chunli , Tang Yi-Da
Published: June 2023

Objective

This study aimed to investigate the relationship between the TyG (Triglyceride-glucose index) and the prognosis of patients with HOCM (hypertrophic obstructive cardiomyopathy) without diabetes.

Research design and methods

A total of 713 eligible patients with HOCM were enrolled in this study and divided into two groups based on treatment: an invasive treatment group (n = 461) and a non-invasive treatment group (n = 252). The patients in both two groups were then divided into three groups based on their TyG index levels. The primary endpoints of this study were Cardiogenic death during long-term follow-up. Kaplan–Meier analysis was used to study the cumulative survival of different groups. Restricted cubic spline was used to model nonlinear relationships between the TyG index and primary endpoints. Myocardial perfusion imaging/Myocardial metabolic imaging examinations were performed to assess glucose metabolism in the ventricular septum of the HOCM patients.

Results

The follow-up time of this study was 41.47 ± 17.63 months. The results showed that patients with higher TyG index levels had better clinical outcomes (HR, 0.215; 95% CI 0.051,0.902; P = 0.036, invasive treatment group; HR, 0.179; 95% CI 0.063,0.508; P = 0.001, non-invasive treatment group). Further analysis showed that glucose metabolism in the ventricular septum was enhanced in HOCM patients.

Conclusions

The findings of this study suggest that the TyG index may serve as a potential protective factor for patients with HOCM without diabetes. The enhanced glucose metabolism in the ventricular septum of HOCM patients may provide a potential explanation for the relationship between the TyG index and HOCM prognosis.
Maternal glycemia in pregnancy is longitudinally associated with blood DNAm variation at the FSD1L gene from birth to 5 years of age
Authors: Taschereau Amélie , Thibeault Kathrine , Allard Catherine , Juvinao-Quintero Diana , Perron Patrice , Lutz Sharon M. , Bouchard Luigi , Hivert Marie-France
Published: June 2023

Background

In utero exposure to maternal hyperglycemia has been associated with an increased risk for the development of chronic diseases in later life. These predispositions may be programmed by fetal DNA methylation (DNAm) changes that persist postnatally. However, although some studies have associated fetal exposure to gestational hyperglycemia with DNAm variations at birth, and metabolic phenotypes in childhood, no study has yet examined how maternal hyperglycemia during pregnancy may be associated with offspring DNAm from birth to five years of age.

Hypothesis

Maternal hyperglycemia is associated with variation in offspring DNAm from birth to 5 years of age.

Methods

We estimated maternal hyperglycemia using the area under the curve for glucose (AUCglu) following an oral glucose tolerance test conducted at 24–30 weeks of pregnancy. We quantified DNAm levels in cord blood (n = 440) and peripheral blood at five years of age (n = 293) using the Infinium MethylationEPIC BeadChip (Illumina). Our total sample included 539 unique dyads (mother–child) with 194 dyads having DNAm at both time-points. We first regressed DNAm M-values against the cell types and child age for each time-point separately to account for the difference by time of measurement for these variables. We then used a random intercept model from the linear mixed model (LMM) framework to assess the longitudinal association between maternal AUCglu and the repeated measures of residuals of DNAm. We adjusted for the following covariates as fixed effects in the random intercept model: maternal age, gravidity, smoking status, child sex, maternal body mass index (BMI) (measured at first trimester of pregnancy), and a binary variable for time-point.

Results

In utero exposure to higher maternal AUCglu was associated with lower offspring blood DNAm levels at cg00967989 located in FSD1L gene (β = − 0.0267, P = 2.13 × 10–8) in adjusted linear regression mixed models. Our study also reports other CpG sites for which DNAm levels were suggestively associated (P < 1.0 × 10–5) with in utero exposure to gestational hyperglycemia. Two of these (cg12140144 and cg07946633) were found in the promotor region of PRDM16 gene (β: − 0.0251, P = 4.37 × 10–07 and β: − 0.0206, P = 2.24 × 10–06, respectively).

Conclusion

Maternal hyperglycemia is associated with offspring DNAm longitudinally assessed from birth to 5 years of age.
On the relationship between mobile-based extramural activities and vocabulary development of EFL learners: a mixed-method study
Authors: Ebadi Saman , Amini Zhila , Gheisari Nouzar
Published: June 2023

Mobile-based extramural English (EE) activities, including watching movies, playing digital games, and listening to music outside the classroom, have played an important role in increasing learners' interest in English as a foreign language (EFL). This mixed-method design study aimed to investigate the role of EE activities in the vocabulary development of intermediate EFL learners. The study included a group of 60 learners, including 30 male and 30 female students from two language institutes. A pretest, posttest, and delayed posttest were used. The experimental group utilized WhatsApp to receive electronic vocabulary instruction four days per week for two months as part of the EE activities. In contrast, the control group received classroom instruction using the conventional approach typically employed in EFL contexts for teaching the same textbook vocabulary. A semi-structured interview was conducted to investigate the participants' beliefs regarding their preference for EE-based activities. The results of the EG group revealed that EE-based activities significantly impacted the students' vocabulary learning (p < 0.001). The findings also revealed no significant differences in vocabulary knowledge between male and female students after using EE activities (p = 0.34). The themes that emerged from the qualitative phase suggested that participants preferred EE-based activities as they can result in less mental stress, more vocabulary learning, improved conversation, and improved pronunciation and grammar. Also, the participants preferred various mobile-based EE activities, including watching movies, listening to music, playing multiple games, watching cartoons, and focusing on movie subtitles, which resulted in their vocabulary development. The findings call for language educators to integrate more virtual and online-based EE activities to supplement traditional vocabulary teaching practices.
The association between permit-to-purchase laws and shootings by police
Authors: Crifasi Cassandra K. , Ward Julie , McCourt Alex D. , Webster Daniel , Doucette Mitchell L.
Published: June 2023

Background

Fatal and nonfatal shootings by police are a public health issue that warrants additional research. Prior research has documented associations between fatal shootings by police and gun ownership, legislative strength scores, and lax concealed carry weapons laws. Despite research on other firearm-related outcomes, little is known about the impact of permit-to-purchase (PTP) laws on shootings by police. We generated counts of fatal and nonfatal OIS from the Gun Violence Archive from 2015 to 2020. We conducted cross-sectional regression modeling with a Poisson distribution and robust standard errors. In addition to PTP, we included several state-level policies that may be associated with shootings by police: comprehensive background check only (CBC-only) laws, concealed carry licensing laws, stand your ground laws, violent misdemeanor prohibitions, and extreme risk protection orders (ERPO). We controlled for state-level demographic characteristics and included a population offset to generate incidence rate ratios (IRR).

Findings

PTP laws were associated with a 28% lower rate in shootings by police [IRR = 0.72, 95% confidence interval (CI) 0.64–0.81]. Shall Issue (IRR = 1.34, 95% CI 1.17–1.53) and Permitless (IRR = 1.61, 95% CI 1.35–1.91) concealed carry laws and CBC-only laws (IRR = 1.12, 95% CI 1.01–1.25) were associated with higher rates of shootings by police. Stand your ground, violent misdemeanor prohibitions, and ERPO laws were not associated with shootings by police.

Conclusions

Our study found that PTP laws were associated with significantly lower rates of shootings by police. Removing restrictions on civilian concealed carry was associated with significantly higher rates. State-level firearm policies may be a lever to address shootings by police.
Efficacy of endotracheal tube clamping to prevent positive airways pressure loss and pressure behavior after reconnection: a bench study
Authors: Bulleri Enrico , Fusi Cristian , Bambi Stefano , Pisani Luigi , Galesi Alice , Rizzello Enrico , Lucchini Alberto , Merlani Paolo , Pagnamenta Alberto
Published: June 2023

Background

Endotracheal tube (ETT) clamping before disconnecting the patient from the mechanical ventilator is routinely performed in patients with acute respiratory distress syndrome (ARDS) to minimize alveolar de-recruitment. Clinical data on the effects of ETT clamping are lacking, and bench data are sparse. We aimed to evaluate the effects of three different types of clamps applied to ETTs of different sizes at different clamping moments during the respiratory cycle and in addition to assess pressure behavior following reconnection to the ventilator after a clamping maneuver.

Methods

A mechanical ventilator was connected to an ASL 5000 lung simulator using an ARDS simulated condition. Airway pressures and lung volumes were measured at three time points (5 s, 15 s and 30 s) after disconnection from the ventilator with different clamps (Klemmer, Chest-Tube and ECMO) on different ETT sizes (internal diameter of 6, 7 and 8 mm) at different clamping moments (end-expiration, end-inspiration and end-inspiration with tidal volume halved). In addition, we recorded airway pressures after reconnection to the ventilator. Pressures and volumes were compared among different clamps, different ETT-sizes and the different moments of clamp during the respiratory cycle.

Results

The efficacy of clamping depended on the type of clamp, the duration of clamping, the size of the ETT and the clamping moment. With an ETT ID 6 mm all clamps showed similar pressure and volume results. With an ETT ID 7 and 8 mm only the ECMO clamp was effective in maintaining stable pressure and volume in the respiratory system during disconnection at all observation times. Clamping with Klemmer and Chest-Tube at end inspiration and at end inspiration with halved tidal volume was more efficient than clamping at end expiration (p < 0.03). After reconnection to the mechanical ventilator, end-inspiratory clamping generated higher alveolar pressures as compared with end-inspiratory clamping with halved tidal volume (p < 0.001).

Conclusions

ECMO was the most effective in preventing significant airway pressure and volume loss independently from tube size and clamp duration. Our findings support the use of ECMO clamp and clamping at end-expiration. ETT clamping at end-inspiration with tidal volume halved could minimize the risk of generating high alveolar pressures following reconnection to the ventilator and loss of airway pressure under PEEP.
Milk kefir drink may not reduce depression in patients with non-alcoholic fatty liver disease: secondary outcome analysis of a randomized, single-blinded, controlled clinical trial
Authors: Mohsenpour Mohammad Ali , Mohammadi Farzaneh , Razmjooei Nadia , Eftekhari Mohammad Hassan , Hejazi Najmeh
Published: June 2023

Background

Depression is prevalent among individuals with non-alcoholic fatty liver disease (NAFLD) and can cause poor health outcomes. Moreover, a solid bilateral association between NAFLD and depression has been shown, which may alleviate by kefir consumption. Thus, we aimed to investigate the effect of milk kefir drinks on the depression status of individuals with NAFLD.

Methods

In a secondary outcome analysis of a randomized, single-blinded, controlled clinical trial, 80 adults with grades 1 to 3 of NAFLD were included in an 8-week intervention. Participants were randomly assigned to Diet or Diet + kefir groups to either follow a low-calorie diet or a low-calorie diet along with a 500 cc milk kefir drink daily. The participants’ demographic, anthropometric, dietary, and physical data were recorded before and after the study. Depression status was assessed using the Persian format of the second version of the Beck Depression Inventory (BDI-II-Persian) at the baseline and after 8 weeks of intervention.

Results

Overall, 80 participants aged 42.87 ± 10.67 years were included in the analysis. The data on the baseline demographic, dietary, and physical activity of the groups were not significantly different. During the study, participants in Diet + Kefir group had a significantly decreased energy (P = 0.02), carbohydrate (P = 0.4), and fat consumption (P = 0.4). However, during the study, the depression score was not significantly reduced in the Diet group, the Diet + Kefir group showed a significant reduction in depression (P = 0.02). However, between-group analyses for changes in depression were not significant (P = 0.59).

Conclusion

Consumption of milk kefir drink for 8 weeks may not reduce depression symptoms in adults with NAFLD.

Trial registration

The trial was registered at IRCT.ir as IRCT20170916036204N6 (August 2018).
Pathobiological analysis of African swine fever virus contact-exposed pigs and estimation of the basic reproduction number of the virus in Vietnam
Authors: Oh Sang-Ik , Bui Ngoc Anh , Bui Vuong Nghia , Dao Duy Tung , Cho Ara , Lee Han Gyu , Jung Young-Hun , Do Yoon Jung , Kim Eunju , Bok Eun-Yeong , Hur Tai-Young , Lee Hu Suk
Published: June 2023

Background

African swine fever (ASF), caused by African swine fever virus (ASFV), is a fatal disease affecting wild and domestic pigs. Since China reported the first ASF outbreak in August 2018, ASFV has swept over the neighbouring Asian countries. However, studies involving experimental pig-to-pig ASFV transmission in Vietnam are lacking. The main objective of this experimental study was to demonstrate the pathobiological characteristics of ASFV contact-exposed pigs and estimate their basic reproduction number (R0) in Vietnam. Fifteen pigs were randomly divided into two groups: experimental (n = 10) and negative control (n = 5) groups. One pig in the experimental group was intramuscularly inoculated with ASFV strain from Vietnam in 2020 and housed with the uninoculated pigs during the study period (28 days).

Results

The inoculated pig died 6 days post-inoculation, and the final survival rate was 90.0%. We started observing viremia and excretion of ASFV 10 days post-exposure in contact-exposed pigs. Unlike the surviving and negative control pigs, all necropsied pigs showed severe congestive splenomegaly and moderate-to-severe haemorrhagic lesions in the lymph nodes. The surviving pig presented with mild haemorrhagic lesions in the spleen and kidneys. We used Susceptible-Infectious-Removed models for estimating R0. The R0 values for exponential growth (EG) and maximum likelihood (ML) were calculated to be 2.916 and 4.015, respectively. In addition, the transmission rates (β) were estimated to be 0.729 (95% confidence interval [CI]: 0.379–1.765) for EG and 1.004 (95% CI: 0.283–2.450) for ML.

Conclusions

This study revealed pathobiological and epidemiological information in about pig-to-pig ASFV transmission. Our findings suggested that culling infected herds within a brief period of time may mitigate the spread of ASF outbreaks.
Giant invasive pituitary adenomas: surgical approach selection paradigm and its influence on the outcome—case series
Authors: Saad Mahmoud , Taha Ahmed Nageeb , Serag Samer , Shata Hosam , Zakaria Wael K.
Published: June 2023

Objective

Pointing out our surgical strategy and experience in selection of surgical approaches in giant pituitary adenomas patients and its relation to surgical and clinical outcome.

Methods

31 patients with giant pituitary adenomas (maximum diameter ≥ 4 cm). We analyzed the preoperative clinical presentation, radiological criteria of the tumor, endocrinological profile, approach selected, extent of resection, clinical outcomes and complications.

Results

16 males (51.6%) and 15 females (48.4%). All the patients had a visual complaint (13 had mild impairment (41.9%), 18 had significant visual loss (58.1%). 20 were nonfunctioning (64.6%), 5 prolactin secreting (16%) and 6 growth hormone secreting (19.4%). Surgical approaches included: standard endoscopic endonasal approach in 7, extended approach in 4, transcranial (extended pterional approach) in 3. Staged endoscopic surgery in 5. Extended pterional approach followed endoscopic approach in 12. Gross total resection in 18 (58%) subtotal resection in 8 patients (25.8%) and partial resection in 5 patients (16.2%). The most common complications was tumor recurrence in 8, CSF leakage in 3, Permanent diabetes insipidus in 2, postoperative hydrocephalus in 1, transient 6th CN palsy in 3, and unfortunately only one patient died. 8 had complete Visual recovery, 9 were improved partially, and 11 remain unchanged. Only 3 showed further deterioration of vision.

Conclusions

Giant invasive pituitary adenoma is still one of the challenging issues in decision making for selection of the appropriate management strategy. Advancement of the endoscopic surgical techniques made the transsphenoidal approach is the primary choice for management of giant pituitary adenoma. However, the door is still opened for transcranial approach as staged the procedure after endoscopic approach or sole approach for some selected cases.
Measurement of superoxide dismutase: clinical usefulness for patients with anti-neutrophil cytoplasmic antibody-associated vasculitis
Authors: Zhang Zhihuan , Huang Wenhan , Ren Feifeng , Luo Lei , Zhou Jun , Tang Lin
Published: June 2023

Objective

To investigate the clinical usefulness of serum superoxide dismutase (SOD) measurement in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).

Methods

In this single-center retrospective study, demographic data, serum SOD levels, erythrocyte sedimentation rate (ESR), C reactive protein (CRP), the Birmingham Vasculitis Activity Score (BVAS), ANCA, organ involvement, and outcomes were analyzed for 152 AAV patients hospitalized in the Second Affiliated Hospital of Chongqing Medical University. Meanwhile, the serum SOD levels of 150 healthy people were collected as the control group.

Results

Compared to the healthy control group, serum SOD levels of the AAV group were significantly lower (P < 0.001). SOD levels of AAV patients were negatively correlated to ESR, CRP, and BVAS (ESR rho = − 0.367, P < 0.001; CRP rho = − 0.590, P < 0.001; BVAS rho = − 0.488, P < 0.001). SOD levels for the MPO-ANCA group were significantly lower than the PR3-ANCA group (P = 0.045). SOD levels for the pulmonary involvement group and the renal involvement group were significantly lower than those for the non-pulmonary involvement group and the non-renal involvement group (P = 0.006; P < 0.001, respectively). SOD levels in the death group were significantly lower than the survival group (P = 0.001).

Conclusions

In AAV patients, low SOD levels might indicate disease associated oxidative stress. SOD levels in AAV patients were decreased with inflammation, suggesting that SOD levels could potentially be a surrogate marker for disease activity. SOD levels in AAV patients were closely related to ANCA serology, pulmonary involvement, and renal involvement, with low SOD levels an important indicator of a poor prognosis for AAV patients.
Maternal- and child-related risk factors for autism during the perinatal period
Authors: Mahboub Samira , Al-Suhaibani Sara , Ellatif Hala Abd , Elkholi Safaa M.
Published: June 2023

Background

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder commonly prevalent in children worldwide including KSA. It causes disability in social interaction, communication, and restrictive and repetitive behaviors. Detecting risk factors for ASD could help initiate screening and risk prevention approaches. Herein, this study aimed to detect several maternal and neonatal risk factors for ASD in KSA.

Results

Ninety-four cases and 282 control completed an online survey tool. The survey items were close-ended questions. Participants were asked about maternal-related risk factors for autism during perinatal period. The logistic regression model revealed having a child diagnosed with autism with two predictors: factors related to the mother and factors related to the baby during perinatal period. The whole model was sig (p < 0.0001). The factors related to the baby have more impact on developing autism than maternal factors (OR is 3 vs 2.3, respectively, p < 0.01 for both).

Conclusion

The findings of this study will be beneficial for subsequent nationwide screenings and educational programs. The study brought to light the potential for identifying children in need of early intervention.
Assessing the accuracy of empirical decline curve techniques for forecasting production in unconventional reservoirs: a case study of Haynesville, Marcellus, and Marcellus Upper Shale
Authors: Coutry Shams , Tantawy Mahmoud , Fadel Sayed
Published: June 2023

Decline curve analysis (DCA) is a widely used method to estimate the production performance and ultimate recovery of conventional and unconventional reservoirs. Due to the unconventional nature of shale wells, traditional decline curve methods are not ideal for analyzing their production decline behavior. In response, different empirical methods have been developed and used which rely on different mathematical and statistical approaches and can result in varying forecasts.

This study compares fourteen decline curve methods, along with the traditional Arps method, in terms of their ability to match production history, sensitivity to data size, effect of flow type, production forecast, and ultimate recovery estimation.

The methods were tested on three wells from Haynesville Shale (Lorikeet Field), Marcellus Shale (Ostrich Field), and Marcellus-Upper Shale (Penguin Field) respectively. The study concludes that each method may be useful in different cases, and engineers should choose the method that best models their wells based on their specific characteristics and circumstances. Recommendations were also provided for an effective evaluation of uncertainty and application of DCA. The primary objective of this study is to improve the accuracy and reliability of DCA predictions for different reservoir types with different declining modes.
Characteristics of rabbit hapten-specific and germline-based BCR repertoires following repeated immunization
Authors: Li Yuan , Kong Yihui , Yu Xuezhi , Yu Wenbo , Wen Kai , Shen Jianzhong , Wang Zhanhui
Published: June 2023

The rabbit is well known for producing diverse antibodies against various antigens including small molecules such as drugs and toxins, due to a robust immune response. Elucidating how hapten repeated immunization shapes the rabbit B cell receptor (BCR) repertoire is crucial to understanding rabbit immune response to small molecules and assisting rare antibody discovery/engineering. In this study, we enriched and sequenced chloramphenicol (CAP)-specific rabbit B cells following repeated immunization, and analyzed both CAP-specific repertoires combined with the structure and affinity features of V1S69/V1S37 germline-based BCRs. The length of rabbit complementarity-determining region 3 of heavy chain (CDRH3) increased after hapten immunization. Repeated immunization significantly reduced the diversity of CAP-specific rabbit BCR clonotypes, and changed the frequency of VDJ usage and the type of V(D)J recombination. The average number of mutations among VL is notably higher than that of VH genes in rabbits, however, they are both not changed along with repeated immunization. Moreover, repeated immunization resulted in an increase surface charge and a decrease in solvent accessible surface area, leading to improvement in the stability of the most abundant V1S69/V1S37 germline-based BCR, along with an affinity increase from an IC50 of 898.2 ng mL−1 at the 1st immunization to 4.16 ng mL−1 at the 6th immunization. The study provides a benchmark for rabbit repertoire-scale analyses and offers a method for antibody discovery of small molecules.
Distinguishing between ICD-11 complex post-traumatic stress disorder and borderline personality disorder: clinical guide and recommendations for future research
Authors: Karatzias Thanos , Bohus Martin , Shevlin Mark , Hyland Philip , Bisson Jonathan I. , Roberts Neil , Cloitre Marylène
Published: June 2023

Although complex post-traumatic stress disorder and borderline personality disorder are distinct disorders, there is confusion in clinical practice regarding the similarities between the diagnostic profiles of these conditions. We summarise the differences in the diagnostic criteria that are clinically informative and we illustrate these with case studies to enable diagnostic accuracy in clinical practice.
Safety, Tolerability, and Antitumor Activity of Zipalertinib Among Patients With Non–Small-Cell Lung Cancer Harboring Epidermal Growth Factor Receptor Exon 20 Insertions
Authors: Piotrowska Zofia , Tan Daniel Shao-Weng , Smit Egbert F. , Spira Alexander I. , Soo Ross A. , Nguyen Danny , Lee Victor Ho-Fun , Yang James Chih-Hsin , Velcheti Vamsidhar , Wrangle John M. , Socinski Mark A. , Koczywas Marianna , Janik John E. , Jones Jeffrey , Yu Helena Alexandra
Published: June 2023

PURPOSE

Although several agents targeting epidermal growth factor receptor (
EGFR
) exon 20 insertions (ex20ins) have recently been approved by the US Food and Drug Administration, toxicities related to the inhibition of wild-type (WT)
EGFR
are common with these agents and affect overall tolerability. Zipalertinib (CLN-081, TAS6417) is an oral EGFR tyrosine kinase inhibitor (TKI) with a novel pyrrolopyrimidine scaffold leading to enhanced selectivity for
EGFR
ex20ins-mutant versus WT
EGFR
with potent inhibition of cell growth in
EGFR
ex20ins-positive cell lines.

METHODS

This phase 1/2a study of zipalertinib enrolled patients with recurrent or metastatic
EGFR
ex20ins-mutant non–small-cell lung cancer (NSCLC) previously treated with platinum-based chemotherapy.

RESULTS

Seventy-three patients were treated with zipalertinib at dose levels including 30, 45, 65, 100, and 150 mg orally twice a day. Patients were predominantly female (56%), had a median age of 64 years, and were heavily pretreated (median previous systemic therapies 2, range 1-9). Thirty six percent of patients had received previous non-ex20ins EGFR TKIs and 3/73 (4.1%) patients received previous EGFR ex20ins TKIs. The most frequently reported treatment-related adverse events of any grade included rash (80%), paronychia (32%), diarrhea (30%), and fatigue (21%). No cases of grade 3 or higher drug-related rash or diarrhea were observed at 100 mg twice a day or below. Objective responses occurred across all zipalertinib dose levels tested, with confirmed partial response (PR) observed in 28/73 (38.4%) response-evaluable patients. Confirmed PRs were seen in 16/39 (41%) response-evaluable patients at the dose of 100 mg twice a day.

CONCLUSION

Zipalertinib has encouraging preliminary antitumor activity in heavily pretreated patients with
EGFR
ex20ins-mutant NSCLC, with an acceptable safety profile, including low frequency of high-grade diarrhea and rash.
Practices and Views of US Oncologists and Genetic Counselors Regarding Patient Recontact After Variant Reclassification: Results of a Nationwide Survey
Authors: Makhnoon Sukh , Davidson Elenita , Shirts Brian , Arun Banu , Shete Sanjay
Published: June 2023

PURPOSE

Over a 5-year or 10-year period, between 6% and 15% of germline cancer genetic variants undergo reclassification. Up-to-date interpretation can clarify a variant's clinical significance and guide patient management. As the frequency of reclassifications increase, the issue of whether, how, when, and which providers should recontact patients with information about reclassification becomes important. However, the field lacks research evidence and definitive guidance from professional organizations about how providers should recontact patients. We compared the perspectives of US oncologists and cancer genetic counselors (GCs) to describe their practices and views regarding recontact.

MATERIALS AND METHODS

We developed a survey using themes identified from semistructured interviews with oncologists and GCs and administered it in a national sample of oncologists and GCs between July and September 2022.

RESULTS

In total, 634 respondents completed the survey including 349 oncologists and 285 GCs. On frequency of recontacting patients with reclassified results, 40% of GCs reported recontacting often compared with 12.5% of oncologists. Neither group reported recording patient preference for recontact on electronic medical record (EMR). Both groups agreed that all reclassified variants, even those that do not affect clinical management, should be returned to patients. They also reported that recontact via EMR messages, mailed letters, and phone calls from GC assistants were more suitable for downgrades. By contrast, face-to-face meetings and phone calls were preferred for upgrades. Remarkably, oncologists were more likely to endorse face-to-face return of results and were more likely to endorse return through a nongenetics provider compared to GCs.

CONCLUSION

These data on current recontact practices and opinions provide a foundation for developing guidelines with explicit recommendations on patient recontact that can help maximize clinical effect while considering provider preferences for recontact within resource-constrained genomic practice settings.
Testosterone Replacement Therapy in Relation With Cardiovascular Disease in Cisgender Women and Transgender People
Authors: Lopez David S , Mulla Juwairia S , El Haddad Danielle , Tahashilder Md Ibrahim , Polychronopolou Efstathia , Baillargeon Jacques , Kuo Yong-Fang , Gilani Syed , Khalife Wissam I
Published: June 2023

Aims

This study aimed to investigate the association of testosterone replacement therapy (TTh) with risk of cardiovascular disease (CVD), and CVD-specific outcomes, in cisgender women and transgender population, and to determine whether this association varies by menopausal status.

Methods

In 25 796 cisgender women and 1580 transgender people (≥30 years old) who were enrolled in the Optum's deidentified Clinformatics Data Mart Database (2007-2021), we identified 6288 pre- and postmenopausal cisgender women and 262 transgender people diagnosed with incident composite of CVD (coronary artery disease [CAD], congestive heart failure, stroke, and myocardial infarction). Prediagnostic prescription of TTh was ascertained for this analysis. Multivariable adjusted Cox proportional hazards models were used to examine the independent association of TTh with incident CVD.

Results

We found a 24% increased risk of CVD (hazard ratio [HR] = 1.24; 95% CI, 1.15-1.34), 26% risk of CAD (HR = 1.26; 95% CI, 1.14-1.39), and a 29% risk of stroke (HR = 1.29; 95% CI, 1.14-1.45) after comparing cisgender women who used TTh with nonusers. Stratification by age group showed similar effects of TTh on CVD, CAD, and stroke. Among transgender people, TTh did not increase the risk of composite CVD, including by age stratification.

Conclusion

Use of TTh increased the risk of CVD, CAD, and stroke among cisgender women but not among transgender people. TTh is becoming more widely accepted in women, and it is the main medical treatment for transgender males. Therefore, use of TTh should be further investigated for the prevention of CVD.
Chromatin Organization and Transcriptional Programming of Breast Cancer Cell Identity
Authors: Bobbitt Jessica R , Seachrist Darcie D , Keri Ruth A
Published: June 2023

The advent of sequencing technologies for assessing chromosome conformations has provided a wealth of information on the organization of the 3-dimensional genome and its role in cancer progression. It is now known that changes in chromatin folding and accessibility can promote aberrant activation or repression of transcriptional programs that can drive tumorigenesis and progression in diverse cancers. This includes breast cancer, which comprises several distinct subtypes defined by their unique transcriptomes that dictate treatment response and patient outcomes. Of these, basal-like breast cancer is an aggressive subtype controlled by a pluripotency-enforcing transcriptome. Meanwhile, the more differentiated luminal subtype of breast cancer is driven by an estrogen receptor-dominated transcriptome that underlies its responsiveness to antihormone therapies and conveys improved patient outcomes. Despite the clear differences in molecular signatures, the genesis of each subtype from normal mammary epithelial cells remains unclear. Recent technical advances have revealed key distinctions in chromatin folding and organization between subtypes that could underlie their transcriptomic and, hence, phenotypic differences. These studies also suggest that proteins controlling particular chromatin states may be useful targets for treating aggressive disease. In this review, we explore the current state of understanding of chromatin architecture in breast cancer subtypes and its potential role in defining their phenotypic characteristics.
Fahr Syndrome Presenting With Status Epilepticus After COVID-19 Infection
Authors: Bitew Helen Yifter , Kambutse Immaculate , Tuyizere Aloys , Claude Gakumba
Published: June 2023

Hypoparathyroidism is a rare metabolic disease. In addition to symptoms of hypocalcemia, chronic hypoparathyroidism can result in brain calcifications leading to Fahr syndrome. Hypoparathyroidism most commonly results as a postsurgical complication, with autoimmune disease the second most common etiology. Here we report a 48-year-old man with symptoms of chronic hypocalcemia who presented with status epilepticus following severe coronavirus disease 2019 (COVID-19) infection. In addition to severe hypocalcemia, he was found to have an inappropriately low serum parathyroid hormone level and basal ganglia calcifications visualized on head computed tomography scan. He was treated with intravenous calcium infusion prior to transition to orally administered calcium, calcitriol, and high-dose cholecalciferol (vitamin D3).
Hunting with heat: thermosensory-driven foraging in mosquitoes, snakes and beetles
Authors: Laursen Willem J. , Tang Ruocong , Garrity Paul A.
Published: June 2023

Animals commonly use thermosensation, the detection of temperature and its variation, for defensive purposes: to maintain appropriate body temperature and to avoid tissue damage. However, some animals also use thermosensation to go on the offensive: to hunt for food. The emergence of heat-dependent foraging behavior has been accompanied by the evolution of diverse thermosensory organs of often exquisite thermosensitivity. These organs detect the heat energy emitted from food sources that range from nearby humans to trees burning in a forest kilometers away. Here, we examine the biophysical considerations, anatomical specializations and molecular mechanisms that underlie heat-driven foraging. We focus on three groups of animals that each meet the challenge of detecting heat from potential food sources in different ways: (1) disease-spreading vector mosquitoes, which seek blood meals from warm-bodied hosts at close range, using warming-inhibited thermosensory neurons responsive to conductive and convective heat flow; (2) snakes (vipers, pythons and boas), which seek warm-blooded prey from ten or more centimeters away, using warmth-activated thermosensory neurons housed in an organ specialized to harvest infrared radiation; and (3) fire beetles, which maximize their offspring's feeding opportunities by seeking forest fires from kilometers away, using mechanosensory neurons housed in an organ specialized to convert infrared radiation into mechanosensory stimuli. These examples highlight the diverse ways in which animals exploit the heat emanating from potential food sources, whether this heat reflects ongoing metabolic activity or a recent lightning strike, to secure a nutritious meal for themselves or for their offspring.
Optimal Monetary Policy According to HANK
Authors: Acharya Sushant , Challe Edouard , Dogra Keshav
Published: June 2023

We study optimal monetary policy in an analytically tractable heterogeneous agent New Keynesian model with rich cross-sectional heterogeneity. Optimal policy differs from a representative agent benchmark because monetary policy can affect consumption inequality, by stabilizing consumption risk arising from both idiosyncratic shocks and unequal exposures to aggregate shocks. The trade-off between consumption inequality, productive efficiency, and price stability is summarized in a simple linear-quadratic problem yielding interpretable target criteria. Stabilizing consumption inequality requires putting some weight on stabilizing the level of output, and correspondingly reducing the weights on the output gap and price level relative to the representative agent benchmark. (JEL E12, E23, E31, E32, E52, E62)
Confidence, Self-Selection, and Bias in the Aggregate
Authors: Enke Benjamin , Graeber Thomas , Oprea Ryan
Published: June 2023

The influence of behavioral biases on aggregate outcomes depends in part on self-selection: whether rational people opt more strongly into aggregate interactions than biased individuals. In betting market, auction and committee experiments, we document that some errors are strongly reduced through self-selection, while others are not affected at all or even amplified. A large part of this variation is explained by differences in the relationship between confidence and performance. In some tasks, they are positively correlated, such that self-selection attenuates errors. In other tasks, rational and biased people are equally confident, such that self-selection has no effects on aggregate quantities. (JEL C91, D44, D91)
Exploring Character Expressions in Comics by Using Stream-Of-Consciousness as 2D animation Production Method
Authors: Yang Min
Published: June 2023

More and more animations are now based on original comics. For instance, some Japanese anime perfectly recreate the original comic drawings in their character expressions, including lines and symbols. However, when these symbols are played in comics, they remain in that scene. As Scott McCloud mentioned in his book Understanding Comics, the definitions of comics and animation differ. Therefore, we cannot stipulate that "sequential visual art" interprets comics or animation (p.7–9). This research uses the fluidity of the stream-of-consciousness concept to make experimental animations with flowing character expressions. It combines comic and animation techniques; if the characters" expressions remain the same, add comic symbols to change them. It also examines whether the audience appreciates that small details can change a character's mood. In other words, characters' expressions constantly change, but the symbols that express this do not change. What kind of experience will this bring? Alternatively, designers create new signs to express feelings and ascertain if the audience understands the character's emotions. Since the critical element is not the character's interactions but the character itself, this research would be helpful for researchers who want to examine a non-narrative, non-dialogue animation and benefit those interested in studying stream-of-consciousness animation techniques.
Χιόνι … στην πόλη, αναπαραστάσεις μεταναστών στον ελληνικό κινηματογράφο
Authors: Δαμάλα Παρασκευή
Published: June 2023

Η παρούσα εργασία επιχειρεί να καταγράψει την αναπαράσταση στον ελληνικό κινηματογράφο του φαινομένου της μετανάστευσης. Αρχικά αναφέρει τον τρόπο με τον οποίο ο παγκόσμιος κινηματογράφος ασχολείται με το φαινόμενο και στη συνέχεια περιγράφει τον τρόπο που ο ελληνικός κινηματογράφος το προσέγγισε. Τέλος αναλύονται δυο ταινίες του νέου ελληνικού κινηματογράφου που περιγράφουν ιστορίες μεταναστών στην Ελλάδα.
Προγνωστικοί παράγοντες εμφανίσεως και δυνατότητα πρόληψης του μετεγχειρητικού υποπαραθυρεοειδισμού
Authors: Δασκαλάκη Άννα
Published: June 2023

2. ΠερίληψηΥπόβαθρο μελέτης: Η μετεγχειρητική υπασβεστιαιμία είναι μια από τις πιο συχνές επιπλοκές μετά από ολική θυρεοειδεκτομή. Τα επίπεδα παραθορμόνης (PTH) και ασβεστίου, που έχουν ληφθεί αρκετές ώρες μετά την επέμβαση, έχουν προταθεί ως σημαντικοί δείκτες για την ανίχνευση ασθενών που δυνητικά θα μπορούσαν να αναπτύξουν μετά-θυρεοειδεκτομή υπασβεστιαιμία. Σκοπός της μελέτης: Να προσδιορίσουμε εάν τα επίπεδα PTH και ασβεστίου που λαμβάνονται άμεσα μετεγχειρητικά και λίγες ώρες μετά, μπορούν να χρησιμοποιηθούν για την έγκαιρη αναγνώριση ασθενών που διατρέχουν κίνδυνο να αναπτύξουν συμπτωματική υπασβεστιαιμία.Μέθοδοι: PTH και ασβέστιο μετρήθηκαν πριν από την επέμβαση,10 λεπτά και 4 ώρες μετά τη θυρεοειδεκτομή, σε 87 ασθενείς. Εκτέλεση: Υπολογίστηκαν τα χαρακτηριστικά απόδοσης μιας σειράς από δείκτες που περιλάμβαναν την PTH και το ασβέστιο καθώς και τους λόγους των μετεγχειρητικών προς τις προεγχειρητικές τιμές τους. Αποτελέσματα: Η τιμή του ασβεστίου τέσσερις ώρες μετά την επέμβαση, ήταν ένας ευαίσθητος (93,75%) αλλά όχι ειδικός (67,61%) δείκτης για να αναδείξει εκείνους τους ασθενείς που δυνητικά θα μπορούσαν να αναπτύξουν συμπτωματική υπασβεστιαιμία. Η αναλογία PTH 4 ωρών / προεγχειρητική ήταν ένας ακριβής (90,81%) αλλά και ο πιο ειδικός (94,37%) δείκτης για τον εντοπισμό των ασθενών που θα μπορούσαν να αναπτύξουν συμπτωματική υπασβεστιαιμία . Η τιμή του ασβεστίου στις 4 ώρες, ο λόγος PTH στις 4 ώρες μετά/προεγχειρητική και η PTH στα 10 λεπτά μετά το χειρουργείο είχαν τις υψηλότερες τιμές στον δείκτη αναλογίας διαγνωστικών πιθανοτήτων (Diagnostic odds ratio / DOR, 50,86, 32,85 και 29.04, αντίστοιχα). Επίσης, ο λόγος PTH 4 ωρών/προεγχειρητική είχε την υψηλότερη (0,694) τιμή σε ότι αφορά τον δείκτη J Youden.Συμπεράσματα: Χαμηλά επίπεδα ασβεστίου ορού 4 ώρες μετά την θυρεοειδεκτομή και ο λόγος PTH 4 ωρών / προεγχειρητική θα μπορούσαν να είναι πολύτιμες προσθήκες στην καθημερινή κλινική πρακτική σε ασθενείς μετά από θυρεοειδεκτομή.