bluuebunny/crossref_metadata_2025_split huggingface dataset:
CRISPR-Cas9 knockout screen informs efficient reduction of the Komagataella phaffii secretome
Authors: Dalvie Neil C. , Lorgeree Timothy R. , Yang Yuchen , Rodriguez-Aponte Sergio A. , Whittaker Charles A. , Hinckley Joshua A. , Clark John J. , Del Rosario Amanda M. , Love Kerry R. , Love J. Christopher 
Published: July 2024

Abstract
Background
The yeast Komagataella phaffii is widely used for manufacturing recombinant proteins, but secreted titers of recombinant proteins could be improved by genetic engineering. In this study, we hypothesized that cellular resources could be redirected from production of endogenous proteins to production of recombinant proteins by deleting unneeded endogenous proteins. In non-model microorganisms such as K. phaffii, however, genetic engineering is limited by lack gene annotation and knowledge of gene essentiality.

Results
We identified a set of endogenous secreted proteins in K. phaffii by mass spectrometry and signal peptide prediction. Our efforts to disrupt these genes were hindered by limited annotation of essential genes. To predict essential genes, therefore, we designed, transformed, and sequenced a pooled library of guide RNAs for CRISPR-Cas9-mediated knockout of all endogenous secreted proteins. We then used predicted gene essentiality to guide iterative disruptions of up to 11 non-essential genes. Engineered strains exhibited a ~20× increase in the production of human serum albumin and a twofold increase in the production of a monoclonal antibody.

Conclusions
We demonstrated that disruption of as few as six genes can increase production of recombinant proteins. Further reduction of the endogenous proteome of K. phaffii may further improve strain performance. The pooled library of secretome-targeted guides for CRISPR-Cas9 and knowledge of gene essentiality reported here will facilitate future efforts to engineer K. phaffii for production of other recombinant proteins and enzymes.
Associations between dietary total antioxidant capacity and sarcopenia: a cross-sectional study
Authors: Aminianfar Azadeh , Hashemi Rezvan , Emami Fatemeh , Heshmat Ramin , Motlagh Ahmadreza Dorosty , Esmaillzadeh Ahmad 
Published: July 2024

Abstract
Background
No study has investigated the relationship between dietary total antioxidant capacity and sarcopenia so far.

Objective
This study aimed to investigate the association between dietary Total Antioxidant Capacity (d-TAC) and sarcopenia in elderly adults.

Methods
In this cross-sectional study we enrolled 300 elderly people (150 men and 150 women) aged ≥ 55 years using cluster random sampling method. Sarcopenia was defined based on European Working Group on Sarcopenia (EWGSOP) definition. A DXA scanner, a squeeze bulb dynamometer and a 4-Meter walk gait speed test was used to measure Appendicular Skeletal Muscle (ASM), muscle strength and muscle performance respectively. We also used a Block-format 117-item food frequency questionnaire (FFQ) to assess dietary intakes of participants. Multivariable logistic regression models were applied to examine the association between d-TAC and sarcopenia.

Results
Mean ± SD age of study participants and their BMI was 66.8 ± 7.72 year and 27.3 ± 4.2 kg/m2, respectively. People in the highest tertile of d-TAC had the greatest hand grip strength (11.9 ± 3.63 vs. 10.4 ± 3.55 psi, p = 0.009) and had lower odds of sarcopenia compared with those in the lowest tertile, either before (OR = 0.39; 95% CI: 0.17, 0.88) or after adjustment for potential confounders (OR = 0.33; 95% CI: 0.11, 0.95). No other significant association was seen between d-TAC and components of sarcopenia.

Conclusion
We found an inverse association between dietary total antioxidant capacity and odds of sarcopenia. No significant association was seen between d-TAC and individual components of sarcopenia. Further studies are needed to confirm our findings.
Different trends in suicide rates among foreign residents in Japan and Japanese citizens during the COVID-19 pandemic
Authors: Taniguchi Yuta , Tamiya Nanako , Iwagami Masao , Yamagishi Kazumasa , Miyawaki Atsushi , Masuda Rie , Kihara Tomomi , Komiyama Jun , Tachikawa Hirokazu , Takahashi Hideto , Iso Hiroyasu 
Published: July 2024

Abstract
Background
Suicide rates in Japan have increased during the COVID-19 pandemic, and foreign residents may be more vulnerable to mental stress during such crises. Therefore, we aimed to compare the trends in suicide rates during the COVID-19 pandemic between foreign residents and Japanese citizens.

Methods
Vital statistics of Japan data from January 1, 2016 to December 31, 2021 were used to calculate quarterly sex-specific suicide rates for foreign residents and Japanese citizens. An event-study analysis was conducted to evaluate whether suicide rates during the COVID-19 pandemic increased compared to pre-pandemic estimates; foreign residents and Japanese citizens were compared using difference-in-difference-in-differences estimates.

Results
Between 2016 and 2021, 1,431 foreign residents and 121,610 Japanese citizens died from suicide in Japan. Although the suicide rate for foreign residents was lower than that for Japanese citizens, Korean residents, who comprise approximately half of the foreign decedents, had largely higher suicide rates than Japanese citizens. The event-study analysis indicated that suicide rates increased among foreign residents for both men and women, and continued for men by the end of 2021. In Japanese citizens, after a decline in suicide rates in the second quarter of 2020, suicide rates increased both among men and women, and lasted for women until the fourth quarter of 2021. The difference-in-difference-in-differences analyses confirmed the initial decline in the second quarter of 2020 in suicide rate only in Japanese men and women, and the persistent increase through 2021 in foreign men.

Conclusions
We found differential trends in suicide rates between foreign and Japanese men and women during the COVID-19 pandemic featuring a persistent increase in foreign men. Suicide prevention measures should be focused on these high-risk subpopulations.
PARP-1, EpCAM, and FRα as potential targets for intraoperative detection and delineation of endometriosis: a quantitative tissue expression analysis
Authors: Belmonte Beatrice , Di Lorenzo Giovanni , Mangogna Alessandro , Bortot Barbara , Bertolazzi Giorgio , Sammataro Selene , Merighi Simona , Martorana Anna , Zito Gabriella , Romano Federico , Giorgiutti Anna , Bottin Cristina , Zanconati Fabrizio , Romano Andrea , Ricci Giuseppe , Biffi Stefania 
Published: July 2024

Abstract
Background
Endometriosis is a gynecological disease characterized by the presence of endometrial tissue in abnormal locations, leading to severe symptoms, inflammation, pain, organ dysfunction, and infertility. Surgical removal of endometriosis lesions is crucial for improving pain and fertility outcomes, with the goal of complete lesion removal. This study aimed to analyze the location and expression patterns of poly (ADP-ribose) polymerase 1 (PARP-1), epithelial cell adhesion molecule (EpCAM), and folate receptor alpha (FRα) in endometriosis lesions and evaluate their potential for targeted imaging.

Methods
Gene expression analysis was performed using the Turku endometriosis database (EndometDB). By immunohistochemistry, we investigated the presence and distribution of PARP-1, EpCAM, and FRα in endometriosis foci and adjacent tissue. We also applied an ad hoc platform for the analysis of images to perform a quantitative immunolocalization analysis. Double immunofluorescence analysis was carried out for PARP-1 and EpCAM, as well as for PARP-1 and FRα, to explore the expression of these combined markers within endometriosis foci and their potential simultaneous utilization in surgical treatment.

Results
Gene expression analysis revealed that PARP-1, EpCAM, and FOLR1 (FRα gene) are more highly expressed in endometriotic lesions than in the peritoneum, which served as the control tissue. The results of the immunohistochemical study revealed a significant increase in the expression levels of all three biomarkers inside the endometriosis foci compared to the adjacent tissues. Additionally, the double immunofluorescence analysis consistently demonstrated the presence of PARP-1 in the nucleus and the expression of EpCAM and FRα in the cell membrane and cytoplasm.

Conclusion
Overall, these three markers demonstrate significant potential for effective imaging of endometriosis. In particular, the results emphasize the importance of PARP-1 expression as a possible indicator for distinguishing endometriotic lesions from adjacent tissue. PARP-1, as a potential biomarker for endometriosis, offers promising avenues for further investigation in terms of both pathophysiology and diagnostic-therapeutic approaches.
Carotid body tumor: characteristics and surgical outcome
Authors: Kakamad Fahmi Hussein , Mustafa Mihr Naif , Yasin Shara Wahdaldeen , Xalid Shanga Sherzad , Mohammed Ayoob A. , Othman Snur , Hiwa Dilan S. , Abdullah Hiwa O. , Abdalla Berun A. , Nasralla Hawkar A. , Ahmed Sasan M. , Mustafa Ayman M. , Hassan Shko H. , Hussein Bushra O. 
Published: July 2024

Abstract
Background
Carotid body tumors are uncommon neuroendocrine growths near the carotid bifurcation. While some advocate preoperative embolization to minimize bleeding, others avoid it due to complications. This study shares the experience of a single center in managing patients with carotid body tumors without practicing preoperative embolization.

Methods
This was a cross-sectional study of patients with carotid body tumors managed between 2020 and 2024. Data were collected from the hospital’s registry. When necessary, routine blood tests, neck ultrasonography, and computed tomography scans were conducted. The tumors were categorized according to Shamblin’s classification. The average duration of follow-up was 20 months.

Results
The study involved 25 patients, 22 (88%) females and 3 (12%) males. Their ages ranged from 27 to 85 years old. Twenty (80%) cases presented with neck swelling, and six (24%) had a positive medical history. Tumors were mainly on the right side (52%), with 20 (80%) showing ill-defined neck masses. Tumor sizes ranged from 1.5 to 7 cm, with Shamblin type II tumors being discovered in the majority of cases (72%). Types of tumors were significantly associated with the tumor size (p-value < 0.05). Blood transfusion was required in five cases (20%), three from type III and two from type II, with none from type I (p-value = 0.001). Temporary neurological deficits occurred in 3 cases (12%). No functional impairment or mortality was recorded.

Conclusions
Carotid body tumors are rare tumors with an unknown etiology. Operation without practicing preoperative embolization may be feasible with an acceptable outcome.
In silico insights into the design of novel NR2B-selective NMDA receptor antagonists: QSAR modeling, ADME-toxicity predictions, molecular docking, and molecular dynamics investigations
Authors: El fadili Mohamed , Er-rajy Mohammed , Mujwar Somdutt , Ajala Abduljelil , Bouzammit Rachid , Kara Mohammed , Abuelizz Hatem A. , Er-rahmani Sara , Elhallaoui Menana 
Published: July 2024

AbstractBased on a structural family of thirty-two NR2B-selective N-Methyl-D-Aspartate receptor (NMDAR) antagonists, two phenylpiperazine derivatives labeled C37 and C39 were conceived thanks to molecular modeling techniques, as novel NMDAR inhibitors exhibiting the highest analgesic activities (of pIC50 order) against neuropathic pain, with excellent ADME-toxicity profiles, and good levels of molecular stability towards the targeted protein of NMDA receptor. Initially, the quantitative structure-activity relationships (QSARs) models were developed using multiple linear regression (MLR), partial least square regression (PLSR), multiple non-linear regression (MNLR), and artificial neural network (ANN) techniques, revealing that analgesic activity was strongly correlated with dipole moment, octanol/water partition coefficient, Oxygen mass percentage, electronegativity, and energy of the lowest unoccupied molecular orbital, whose the correlation coefficients of generated models were: 0.860, 0.758, 0.885 and 0.977, respectively. The predictive capacity of each model was evaluated by an external validation with correlation coefficients of 0.703, 0.851, 0.778, and 0.981 respectively, followed by a cross-validation technique with the leave-one-out procedure (CVLOO) with Q2cv of 0.785, more than Y-randomization test, and applicability domain (AD), in addition to Fisher’s and Student’s statistical tests. Thereafter, ten novel molecules were designed based on MLR QSAR model, then predicted with their ADME-Toxicity profiles and subsequently examined for their similarity to the drug candidates. Finally, two of the most active compounds (C37 and C39) were chosen for molecular docking and molecular dynamics (MD) investigations during 100 ns of MD simulation time in complex with the targeted protein of NMDA receptor (5EWJ.pdb).
Pricing of insurance-linked securities: a multi-peril approach
Authors: Burnecki Krzysztof , Teuerle Marek A. , Zdeb Martyna 
Published: July 2024

AbstractIn this paper we build a methodology for pricing of insurance-linked securities which are tied to multiple natural catastrophe perils. As a representative example, we construct a multi-peril catastrophe (CAT) bond which can be linked to the industry loss indices or actual losses incurred by an insurer. We provide pricing formulas for such CAT bonds. We illustrate the introduced methodology on the US natural catastrophe data obtained from Property Claim Services (PCS). Within this dataset, we specifically examine two types of risks: losses associated with wind and thunderstorm events, and those linked to winter storm events. Then, we fit and validate the underlying compound non-homogeneous Poisson processes taking into account the fact that the data are left-truncated. The best fitted loss distributions appear to be Burr and Generalised Extreme Value and for the first peril and log-normal for the second. Finally, we visualise the zero-coupon CAT bond prices for the selected best-fitted models.
Ultrasound-guided perineural injection of the saphenous nerve in goat cadavers
Authors: Torruella Xavier , Puggioni Antonella , Santos Bruno , Brama Pieter , Huuskonen Vilhelmiina 
Published: July 2024

Abstract
Background
Surgery of the goat stifle joint requires good perioperative analgesia, ideally without affecting motor function in the postoperative period.
The objective of this study was to describe an ultrasound-guided technique for saphenous nerve block in goats. Eleven fresh female goat cadavers from two different age groups were used: seven of them were four years old with a mean ± SD body weight of 65.9 ± 7.3 kg. Four animals were six months old and their mean ± SD body weight was 20.1 ± 3.1 kg. The cadavers were positioned in lateral recumbency with the limb to be blocked lowermost. A high-frequency linear transducer (6–12 MHz) was used to localise the interfascial plane between the sartorius and the vastus medialis muscles and to identify the saphenous nerve on the medial aspect of the thigh, caudal to the femur, at the level of the femoral triangle. In 22 pelvic limbs 0.1 mL/kg of methylene blue was injected around the saphenous nerve under ultrasound guidance, followed by gross anatomical dissection. The length of circumferentially stained nerve was measured, and the success rate of achieving at least 1 cm of staining is presented with a 95% confidence interval (CI).

Results
Although not all saphenous nerves were sonographically identified, their boundaries were defined as cranial to the femoral artery, lateral to the sartorius muscle, and medial to the vastus medialis and rectus femoris muscles, within the perivascular fat. During anatomical dissection, the overall dye solution distribution was graded as complete in 17/22 limbs indicating a 77.3% success rate [95% CI (0.598, 0.948)], partial in 3/22 limbs and failed in 2/22 limbs.

Conclusions
The success rate of this study indicates the feasibility of employing the ultrasound-guided technique to perform saphenous nerve block in goats. However, further in-vivo studies are recommended to assess the block's clinical efficacy before implementation on clinical patients.
Comparative stagewise mapping of trace elements using ICP-OES in five Ayurvedic Marine Drugs highlights their posologic and clinical implications
Authors: Chavan Sandeep Bhagwan , Walunj Tanhaji Balu , Gupta Vidya Shrikant , Deshmukh Vineeta Vasant , Sardeshmukh Sadanand Prabhakar 
Published: July 2024

AbstractRasashastra, an Ayurvedic pharmaceutical branch, scientifically converts natural resources into palatable therapeutic dosage forms. Ayurvedic Marine Drugs (AMD) are mainly calcium carbonate/ calcite, but in Ayurvedic treatment modality they are uniquely used for several ailments. Moreover, their detailed microchemical compositions have seldom been reported. In this study, five raw materials, conch, oyster shell, cowry, coral, and pearl, their transitions during the manufacturing process, and the final drugs were analyzed for identification and quantitation of minor elements using a validated inductively coupled plasma optical emission spectrophotometry method. All the five raw materials contained traces of Al, Ag, B, Ba, Cu, Co, Cr, Fe, Hg, Li, K, Mg, Mn, Na, Ni, Pb, S, Sr, Tl, and Zn. Interestingly, B, Co, Cr, Li, Mn, and Ni were absent in the finished products, whereas Pb and Hg exhibited a considerable decrement during the drug formation. The first three components of principal component analysis together explained 72.09% of variance. Raw AMD indicated positive factor scores, whereas their respective purified and incinerated forms exhibited negative scores. Cluster analysis derived a dendrogram typically forming incinerated AMD group but not for the raw forms. Coral with Mg as highest content was a remarkable outlier in both these analyses as compared to Na in others. In discriminant analysis of the presence/absence of elements and periodic table-based classifications, coral and pearl showed higher variation indicating as discriminants when equated with others. Periodic table-based classification was a better model for discrimination. Correlation analysis in both classifications revealed a strong correlation of conch with oyster shells and vice versa, cowry and pearl with oyster shell and a weak correlation of coral with pearl. Coral was a good predictor followed by conch, pearl, oyster shell, and cowry, sequentially, and can be considered a moderately sensitive but highly specific model. Thus, ICP-OES technique is highly precise and accurate for assessing the micro-composition of raw, in-process, and finished products to ensure their transitions, quality, and genuineness. Such characterized traditional medicines should be further investigated in depth for their mechanistic aspects.
Graphical abstract
A comparison of 2D and 3D magnetic resonance imaging-based intratumoral and peritumoral radiomics models for the prognostic prediction of endometrial cancer: a pilot study
Authors: Yan Ruixin , Qin Siyuan , Xu Jiajia , Zhao Weili , Xin Peijin , Xing Xiaoying , Lang Ning 
Published: July 2024

Abstract
Background
Accurate prognostic assessment is vital for the personalized treatment of endometrial cancer (EC). Although radiomics models have demonstrated prognostic potential in EC, the impact of region of interest (ROI) delineation strategies and the clinical significance of peritumoral features remain uncertain. Our study thereby aimed to explore the predictive performance of varying radiomics models for the prediction of LVSI, DMI, and disease stage in EC.

Methods
Patients with 174 histopathology-confirmed EC were retrospectively reviewed. ROIs were manually delineated using the 2D and 3D approach on T2-weighted MRI images. Six radiomics models involving intratumoral (2Dintra and 3Dintra), peritumoral (2Dperi and 3Dperi), and combined models (2Dintra + peri and 3Dintra + peri) were developed. Models were constructed using the logistic regression method with five-fold cross-validation. Area under the receiver operating characteristic curve (AUC) was assessed, and was compared using the Delong’s test.

Results
No significant differences in AUC were observed between the 2Dintra and 3Dintra models, or the 2Dperi and 3Dperi models in all prediction tasks (P > 0.05). Significant difference was observed between the 3Dintra and 3Dperi models for LVSI (0.738 vs. 0.805) and DMI prediction (0.719 vs. 0.804). The 3Dintra + peri models demonstrated significantly better predictive performance in all 3 prediction tasks compared to the 3Dintra model in both the training and validation cohorts (P < 0.05).

Conclusions
Comparable predictive performance was observed between the 2D and 3D models. Combined models significantly improved predictive performance, especially with 3D delineation, suggesting that intra- and peritumoral features can provide complementary information for comprehensive prognostication of EC.
The development of 177Lu-DOTA-CC-PSMA following a unified “Click Chemistry” protocol of synthesizing metal nuclide-conjugated radiopharmaceuticals
Authors: Zheng Xiaobei , Xue Shuai , Zhao Zhongqi , Jin Shuxin , He Shuhua , Jia Lina , Li Zheng , Vanhove Christian , De Vos Filip , Kuang Zijun , Wang Tiantian , Neyt Sara , Zhang Lan , Li Xiao 
Published: July 2024

Abstract
Background
Currently, the synthesis pathway of metal nuclide-labeled radiopharmaceuticals is mainly divided into two steps: first, connecting the chelator with the target molecule, and second, labeling the metal nuclide to the chelator. However, the second step of the reaction to label the metal nuclide requires high temperature (90–100 °C), which tends to denature and inactivate the target molecule, leading to loss of biological activities, especially the targeting ability. A feasible solution may be the click chemistry labeling method, which consists of reacting a metal nuclide with a chelating agent to generate an intermediate and then synthesizing a radiopharmaceutical agent via the click chemistry intermediate and the target molecule-alkyne compound. In this study, through the click chemistry of 177Lu-DOTA-N3 with prostate-specific membrane antigen (PSMA)-alkyne compound, 177Lu-labeled PSMA-targeted molecular probe was synthesized and evaluated for its potential to be cleared from the bloodstream and rapidly distributed to tissues and organs, achieving a high target/non-target ratio. 177Lu-PSMA-617 was utilized as an analogue for comparison in terms of synthesizing efficiency and PSMA-targeting ability.

Results
A novel 177Lu-labeled PSMA radioligand was successfully synthesized through the click chemistry of 177Lu-DOTA-N3 with PSMA-alkyne compound, and abbreviated as 177Lu-DOTA-CC-PSMA, achieving a radiochemical yield of 77.07% ± 0.03% (n = 6) and a radiochemical purity of 97.62% ± 1.49% (n = 6) when purified by SepPak C18 column. Notably, 177Lu-DOTA-CC-PSMA was characterized as a hydrophilic compound that exhibited stability at room temperature and commendable pharmacokinetic properties, such as the superior uptake (19.75 ± 3.02%ID/g at 0.5 h) and retention (9.14 ± 3.16%ID/g at 24 h) within xenografts of 22Rv1 tumor-bearing mice. SPECT/CT imaging indicated that radioactivity in both kidneys and bladder was essentially eliminated after 24 h, while 177Lu-DOTA-CC-PSMA was further enriched and retained in PSMA-expressing tumors, resulting in the high target/non-target ratio.

Conclusion
This study demonstrated the potential of click chemistry to unify the synthesis of metal radiopharmaceuticals, and 177Lu-DOTA-CC-PSMA was found for rapid clearance and appropriate chemical stability as a PSMA-targeted radioligand.