bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gastrointestinal perforation after bevacizumab: a multi-site, single-institution study with a focus on survival
Authors: Storandt Michael H. , Tran Nguyen H. , Ehret Christopher J. , Hanna Mina , Jochum Jacob , Moynagh Michael R. , Jatoi Aminah 
Published: June 2023

Abstract
Background
Bevacizumab-induced gastrointestinal perforation is a rare but potentially devastating adverse event that has generated limited data on overall survival. Yet, such survival data are critical in guiding management.

Methods
This multi-site, single-institution retrospective study focused on all cancer patients who had received bevacizumab and who had suffered a well-documented gastrointestinal perforation from January 1, 2004 through January 20, 2022.The main goal was to report survival outcomes; Kaplan Meier curves and Cox survival models were used for this purpose.

Results
Eighty-nine patients are included in this report with a median age of 62 years (range 26–85). Colorectal cancer was the most common malignancy (n = 42). Thirty-nine patients underwent surgery for the perforation. Seventy-eight were deceased at the time of reporting with an overall median survival of all patients of 2.7 months (range 0–45 months), and 32 (36%) died within 30 days of perforation. In univariable survival analyses, no statistically significant associations were observed for age, gender, corticosteroid use, and time since last bevacizumab dose. However, surgically treated patients manifested a better survival (hazard ratio (HR) 0.49 (95% CI 0.31–0.78); p = 0.003). In multivariable analyses, surgery continued to be associated with improved survival (HR 0.47 (95% CI 0.29–0.74); p = 0.002), and corticosteroid use was associated with worse survival (HR 1.75 (95% CI 1.02–2.99); p = 0.04).

Conclusion
Although gastrointestinal perforation after bevacizumab should be managed on a case-by-case basis, these descriptive survival data can help inform patients, their families, and healthcare providers as challenging management decisions arise.
Preparation of the endometrium for frozen embryo transfer: an update on clinical practices
Authors: Zhang Yiting , Fu Xiao , Gao Shuli , Gao Shuzhe , Gao Shanshan , Ma Jinlong , Chen Zi-Jiang 
Published: June 2023

AbstractOver the past decade, the application of frozen-thawed embryo transfer treatment cycles has increased substantially. Hormone replacement therapy and the natural cycle are two popular methods for preparing the endometrium. Hormone replacement therapy is now used at the discretion of the doctors because it is easy to coordinate the timing of embryo thawing and transfer with the schedules of the in-vitro fertilization lab, the treating doctors, and the patient. However, current results suggest that establishing a pregnancy in the absence of a corpus luteum as a result of anovulation may pose significant maternal and fetal risks. Therefore, a ‘back to nature’ approach that advocates an expanded use of natural cycle FET in ovulatory women has been suggested. Currently, there is increasing interest in how the method of endometrial preparation may influence frozen embryo transfer outcomes specifically, especially when it comes to details such as different types of ovulation monitoring and different luteal support in natural cycles, and the ideal exogenous hormone administration route as well as the endocrine monitoring in hormone replacement cycles. In addition to improving implantation rates and ensuring the safety of the fetus, addressing these points will allow for individualized endometrial preparation, also as few cycles as possible would be canceled.
Simplified predictive scores for thrombosis and bleeding complications in newly diagnosed acute leukemia patients
Authors: Owattanapanich Weerapat , Rungjirajittranon Tarinee , Jantataeme Apichaya , Kungwankiattichai Smith , Ruchutrakool Theera 
Published: June 2023

Abstract
Background
Bleeding and thrombotic complications are the leading causes of death in acute leukemia patients. The Conventional International Society of Thrombosis and Haemostasis Disseminated Intravascular Coagulation (ISTH DIC) scoring system is utilized to assess DIC diagnoses in various conditions. Nevertheless, limited studies have tested the system’s accuracy in predicting thrombo-hemorrhagic events in individuals with acute leukemia. This study aimed to (1) validate the ISTH DIC scoring system and (2) propose a new Siriraj Acute Myeloid/Lymphoblastic Leukemia (SiAML) bleeding and thrombosis scoring system for thrombohemorrhagic risk assessment in acute leukemia.

Methods
We conducted a retro-prospective observational study of newly diagnosed acute leukemia patients between March 2014 and December 2019. We recorded thrombohemorrhagic episodes within 30 days postdiagnosis and DIC profiles, including prothrombin time, platelet level, D-dimer, and fibrinogen. The sensitivities, specificities, positive and negative predictive values, and areas under receiver operating characteristic curves for the ISTH DIC and SiAML scoring systems were calculated.

Results
In all, 261 acute leukemia patients were identified: 64% with acute myeloid leukemia, 27% with acute lymphoblastic leukemia, and 9% with acute promyelocytic leukemia. Overall bleeding and thrombotic events were 16.8% and 6.1%, respectively. With a cutoff of 5 for the ISTH DIC score, the sensitivity and specificity for bleeding prediction were 43.5% and 74.4%, respectively, while the corresponding values for thrombotic prediction were 37.5% and 71.8%, respectively. D-dimer > 5000 µg FEU/L and fibrinogen ≤ 150 mg/dL were significantly associated with bleeding. A SiAML-bleeding score was calculated using these factors, with a sensitivity and specificity of 65.2% and 65.6%, respectively. Conversely, D-dimer > 7000 µg FEU/L, platelet > 40 × 109/L, and white blood cell level > 15 × 109/L were significant variables related to thrombosis. Using these variables, we established a SiAML-thrombosis score with a sensitivity and specificity of 93.8% and 66.1%, respectively.

Conclusions
The proposed SiAML scoring system might be valuable for prognosticating individuals at risk for bleeding and thrombotic complications. Prospective validation studies are needed to verify its usefulness.
Pulsatile cerebral paraarterial flow by peristalsis, pressure and directional resistance
Authors: Sharp M. Keith 
Published: June 2023

Abstract
Background
A glymphatic system has been proposed that comprises flow that enters along cerebral paraarterial channels between the artery wall and the surrounding glial layer, continues through the parenchyma, and then exits along similar paravenous channels. The mechanism driving flow through this system is unclear. The pulsatile (oscillatory plus mean) flow measured in the space surrounding the middle cerebral artery (MCA) suggests that peristalsis created by intravascular blood pressure pulses is a candidate for the paraarterial flow in the subarachnoid spaces. However, peristalsis is ineffective in driving significant mean flow when the amplitude of channel wall motion is small, as has been observed in the MCA artery wall. In this paper, peristalsis in combination with two additional mechanisms, a longitudinal pressure gradient and directional flow resistance, is evaluated to match the measured MCA paraarterial oscillatory and mean flows.

Methods
Two analytical models are used that simplify the paraarterial branched network to a long continuous channel with a traveling wave in order to maximize the potential effect of peristalsis on the mean flow. The two models have parallel-plate and annulus geometries, respectively, with and without an added longitudinal pressure gradient. The effect of directional flow resistors was also evaluated for the parallel-plate geometry.

Results
For these models, the measured amplitude of arterial wall motion is too large to cause the small measured amplitude of oscillatory velocity, indicating that the outer wall must also move. At a combined motion matching the measured oscillatory velocity, peristalsis is incapable of driving enough mean flow. Directional flow resistance elements augment the mean flow, but not enough to provide a match. With a steady longitudinal pressure gradient, both oscillatory and mean flows can be matched to the measurements.

Conclusions
These results suggest that peristalsis drives the oscillatory flow in the subarachnoid paraarterial space, but is incapable of driving the mean flow. The effect of directional flow resistors is insufficient to produce a match, but a small longitudinal pressure gradient is capable of creating the mean flow. Additional experiments are needed to confirm whether the outer wall also moves, as well as to validate the pressure gradient.
Comparison of bacterial profiles in human milk from mothers of term and preterm infants
Authors: Miura Kumiko , Tanaka Miori , Date Midori , Ito Mizuho , Mizuno Noriko , Mizuno Katsumi 
Published: June 2023

Abstract
Background
Reducing the disposal of donated human milk (HM) is important for efficient management of human milk banks (HMBs). The presence of bacteria growth is the main factor that contributes to the disposal of donated HM. The bacterial profile in HM is suspected to differ between term and preterm mothers, with HM from preterm mothers containing more bacteria. Thus, elucidation of the causes of bacterial growth in preterm and term HM may help to reduce the disposal of donated preterm HM. This study compared the bacterial profiles of HM between mothers of term infants and mothers of preterm infants.

Methods
This pilot study was conducted in the first Japanese HMB, which was initiated in 2017. This study analyzed 214 human milk samples (term: 75, preterm: 139) donated by 47 registered donors (term: 31, preterm: 16) from January to November 2021. Bacterial culture results in term and preterm HM were retrospectively reviewed in May 2022. Differences in total bacterial count and bacterial species count per batch were analyzed using the Mann–Whitney U test. Bacterial loads were analyzed using the Chi-square test or Fisher’s exact test.

Results
The disposal rate did not significantly differ between term and preterm groups (p = 0.77), but the total amount of disposal was greater in the preterm group (p < 0.01). Coagulase-negative Staphylococci, Staphylococcus aureus, and Pseudomonas fluorescens were frequently found in both types of HM. Serratia liquefaciens (p < 0.001) and two other bacteria were present in term HM; a total of five types of bacteria, including Enterococcus faecalis and Enterobacter aerogenes (p < 0.001) were present in preterm HM. The median (interquartile range) total bacterial counts were 3,930 (435–23,365) colony-forming units (CFU)/mL for term HM and 26,700 (4,050–334,650) CFU/mL for preterm HM (p < 0.001).

Conclusions
This study revealed that HM from preterm mothers had a higher total bacterial count and different types of bacteria than HM from term mothers. Additionally, preterm infants can receive nosocomial-infection-causing bacteria in the NICU through their mother’s milk. Enhanced hygiene instructions for preterm mothers may reduce the disposal of valuable preterm human milk, along with the risk of HM pathogen transmission to infants in NICUs.
The treatment of obesity in children and adolescents: consensus position statement of the Italian society of pediatric endocrinology and diabetology, Italian Society of Pediatrics and Italian Society of Pediatric Surgery
Authors: Maffeis Claudio , Olivieri Francesca , Valerio Giuliana , Verduci Elvira , Licenziati Maria Rosaria , Calcaterra Valeria , Pelizzo Gloria , Salerno Mariacarolina , Staiano Annamaria , Bernasconi Sergio , Buganza Raffaele , Crinò Antonino , Corciulo Nicola , Corica Domenico , Destro Francesca , Di Bonito Procolo , Di Pietro Mario , Di Sessa Anna , deSanctis Luisa , Faienza Maria Felicia , Filannino Grazia , Fintini Danilo , Fornari Elena , Franceschi Roberto , Franco Francesca , Franzese Adriana , Giusti Lia Franca , Grugni Graziano , Iafusco Dario , Iughetti Lorenzo , Lera Riccardo , Limauro Raffaele , Maguolo Alice , Mancioppi Valentina , Manco Melania , Del Giudice Emanuele Miraglia , Morandi Anita , Moro Beatrice , Mozzillo Enza , Rabbone Ivana , Peverelli Paola , Predieri Barbara , Purromuto Salvo , Stagi Stefano , Street Maria Elisabeth , Tanas Rita , Tornese Gianluca , Umano Giuseppina Rosaria , Wasniewska Malgorzata 
Published: June 2023

AbstractThis Position Statement updates the different components of the therapy of obesity (lifestyle intervention, drugs, and surgery) in children and adolescents, previously reported in the consensus position statement on pediatric obesity of the Italian Society of Pediatric Endocrinology and Diabetology and the Italian Society of Pediatrics. Lifestyle intervention is the first step of treatment. In children older than 12 years, pharmacotherapy is the second step, and bariatric surgery is the third one, in selected cases. Novelties are available in the field of the medical treatment of obesity. In particular, new drugs demonstrated their efficacy and safety and have been approved in adolescents. Moreover, several randomized control trials with other drugs are in process and it is likely that some of them will become available in the future. The increase of the portfolio of treatment options for obesity in children and adolescents is promising for a more effective treatment of this disorder.
Synthesis of novel mono- and bis-pyrazolylthiazole derivatives as anti-liver cancer agents through EGFR/HER2 target inhibition
Authors: Salem Mostafa E. , Mahrous Esraa M. , Ragab Eman A. , Nafie Mohamed S. , Dawood Kamal M. 
Published: June 2023

Abstract3-Bromoacetyl-4-(2-naphthoyl)-1-phenyl-1H-pyrazole (6) was synthesized from 2-acetylnaphthalene and was used as a new key building block for constructing the title targets. Thus, the reaction of 6 with the thiosemicarbazones 7a–d and 9–11 afforded the corresponding simple naphthoyl-(3-pyrazolyl)thiazole hybrids 8a–d and 12 ~ 14. The symmetric bis-(2-naphthoyl-pyrazol-3-yl)thiazol-2-yl)hydrazono)methyl)phenoxy)alkanes 18a-c and 21a-c were similarly synthesized from reaction of 6 with the appropriate bis-thiosemicarbazones 17a-c and 19a-c, respectively. The synthesized two series of simple and symmetrical bis-molecular hybrid merging naphthalene, thiazole, and pyrazole were evaluated for their cytotoxicity. Compounds 18b,c and 21a showed the most potent cytotoxicity (IC50 = 0.97–3.57 µM) compared to Lapatinib (IC50 = 7.45 µM). Additionally, they were safe (non-cytotoxic) against the THLE2 cells with higher IC50 values. Compounds 18c exhibited promising EGFR and HER-2 inhibitory activities with IC50 = 4.98 and 9.85 nM, respectively, compared to Lapatinib (IC50 = 6.1 and 17.2 nM). Apoptosis investigation revealed that 18c significantly activated apoptotic cell death in HepG2 cells, increasing the death rate by 63.6-fold and arresting cell proliferation at the S-phase. Compound 18c upregulated P53 by 8.6-fold, Bax by 8.9-fold, caspase-3,8,9 by 9, 2.3, and 7.6-fold, while it inhibited the Bcl-2 expression by 0.34-fold. Thereby, compound 18c exhibited promising cytotoxicity against EGFR/HER2 inhibition against liver cancer.
In-silico engineering of RNA nanoplatforms to promote the diabetic wound healing
Authors: Beheshtizadeh Nima , Salimi Alireza , Golmohammadi Mahsa , Ansari Javad Mohajer , Azami Mahmoud 
Published: June 2023

AbstractOne of the most notable required features of wound healing is the enhancement of angiogenesis, which aids in the acceleration of regeneration. Poor angiogenesis during diabetic wound healing is linked to a shortage of pro-angiogenic or an increase in anti-angiogenic factors. As a result, a potential treatment method is to increase angiogenesis promoters and decrease suppressors. Incorporating microRNAs (miRNAs) and small interfering RNAs (siRNAs), two forms of quite small RNA molecules, is one way to make use of RNA interference. Several different types of antagomirs and siRNAs are now in the works to counteract the negative effects of miRNAs. The purpose of this research is to locate novel antagonists for miRNAs and siRNAs that target multiple genes to promote angiogenesis and wound healing in diabetic ulcers.In this context, we used gene ontology analysis by exploring across several datasets. Following data analysis, it was processed using a systems biology approach. The feasibility of incorporating the proposed siRNAs and miRNA antagomirs into polymeric bioresponsive nanocarriers for wound delivery was further investigated by means of a molecular dynamics (MD) simulation study. Among the three nanocarriers tested (Poly (lactic-co-glycolic acid) (PLGA), Polyethylenimine (PEI), and Chitosan (CTS), MD simulations show that the integration of PLGA/hsa-mir-422a is the most stable (total energy = -1202.62 KJ/mol, Gyration radius = 2.154 nm, and solvent-accessible surface area = 408.416 nm2). With values of -25.437 KJ/mol, 0.047 nm for the Gyration radius, and 204.563 nm2 for the SASA, the integration of the second siRNA/ Chitosan took the last place. The results of the systems biology and MD simulations show that the suggested RNA may be delivered through bioresponsive nanocarriers to speed up wound healing by boosting angiogenesis.
Driving the conversion of phytosterol to 9α-hydroxy-4-androstene-3,17-dione in Mycolicibacterium neoaurum by engineering the supply and regeneration of flavin adenine dinucleotide
Authors: Song Lu , Ke Jie , Luo Zhi-Kun , Xiong Liang-Bin , Dong Yu-Guo , Wei Dong-Zhi , Wang Feng-Qing 
Published: June 2023

Abstract
Background
The conversion of phytosterols to steroid synthons by engineered Mycolicibacteria comprises one of the core steps in the commercial production of steroid hormones. This is a complex oxidative catabolic process, and taking the production of androstenones as example, it requires about 10 equivalent flavin adenine dinucleotide (FAD). As the high demand for FAD, the insufficient supply of FAD may be a common issue limiting the conversion process.

Results
We substantiated, using the production of 9α-hydroxy-4-androstene-3,17-dione (9-OHAD) as a model, that increasing intracellular FAD supply could effectively increase the conversion of phytosterols into 9-OHAD. Overexpressing ribB and ribC, two key genes involving in FAD synthesis, could significantly enhance the amount of intracellular FAD by 167.4% and the production of 9-OHAD by 25.6%. Subsequently, styrene monooxygenase NfStyA2B from Nocardia farcinica was employed to promote the cyclic regeneration of FAD by coupling the oxidation of nicotinamide adenine dinucleotide (NADH) to NAD+, and the production of 9-OHAD was further enhanced by 9.4%. However, the viable cell numbers decreased by 20.1%, which was attributed to sharply increased levels of H2O2 because of the regeneration of FAD from FADH2. Thus, we tried to resolve the conflict between FAD regeneration and cell growth by the overexpression of catalase and promotor replacement. Finally, a robust strain NF-P2 was obtained, which could produce 9.02 g/L 9-OHAD after adding 15 g/L phytosterols with productivity of 0.075 g/(L h), which was 66.7% higher than that produced by the original strain.

Conclusions
This study highlighted that the cofactor engineering, including the supply and recycling of FAD and NAD+ in Mycolicibacterium, should be adopted as a parallel strategy with pathway engineering to improve the productivity of the industrial strains in the conversion of phytosterols into steroid synthons.
Feline heartworm disease and environmental allergens hypersensitivity: is there a link?
Authors: García-Rodríguez Sara N. , Costa-Rodríguez Noelia , Matos Jorge I. , Falcón-Cordón Yaiza , Morchón Rodrigo , Carretón Elena , Montoya-Alonso José A. 
Published: June 2023

Abstract
Background
Cats can be infected by Dirofilaria immitis, the causative agent of heartworm disease, characterized by respiratory signs, airway hyperreactivity, remodelling and inflammation. Allergy is a multifactorial pathology, and the role of a number of helminth parasites in the development of allergies in humans and other species has been demonstrated in many studies. The aim of the present study was to verify whether cats seropositive for D. immitis present hypersensitivity to some environmental allergens.

Methods
Blood samples were collected from 120 cats and tested for the presence of specific immunoglobulin G antibodies against D. immitis and for hypersensitivity to 20 allergens, using commercial allergen test kits.

Results
Of the 120 cats tested, 72 (60.0%) were seropositive for anti-D. immitis IgG and 55 (45.8%) showed clinical signs of heartworm disease of a respiratory nature. The results of testing with the allergen kits showed that 50.8% of cats were seropositive for ≥ 1 allergens, with the most common allergens being Dermatophagoides farinae (25.8%), Dermatophagoides pteronyssinus (20.0%), Malassezia (17.5%) and Ctenocephalides felis (14.2%). The prevalence of allergies was significantly higher—by almost threefold—in cats seropositive for D. immitis (68.1% vs. 25%). There were no significant differences between the prevalence of allergic cats and presence/absence of symptoms, and the results confirmed that symptoms were not a decisive factor for the presence of allergies. The risk for developing allergies was 6.3-fold higher in cats seropositive for D. immitis than in cats that were seronegative, confirming that seropositivity for D. immitis is a risk factor.

Conclusions
Cats with confirmed heartworm can develop serious respiratory signs, potentially leading to progression to permanent lung injury and predisposing cats to hyperresponsive airway disease. Previous studies have shown that seropositivity for D. immitis and Wolbachia is related to the presence of bronchoconstriction and bronchospasm in the affected cat. The results support the suspicion that contact with D. immitis may be a risk factor for the presence of allergies.

Graphical abstract
Why is Babesia not killed by artemisinin like Plasmodium?
Authors: Si Wenwen , Fang Chuantao , Liu Chuang , Yin Meng , Xu Wenyue , Li Yanna , Yan Xiaoli , Shen Yujuan , Cao Jianping , Sun Jun 
Published: June 2023

AbstractBabesia spp. are intraerythrocytic apicomplexans that digest and utilize red blood cells in a similar way to intraerythrocytic Plasmodium spp., but unlike the latter, are not sensitive to artemisinin. A comparison of Babesia and Plasmodium genomes revealed that Babesia genomes, which are smaller than those of Plasmodium, lack numerous genes, and especially haem synthesis-related genes, that are found in the latter. Single-cell sequencing analysis showed that the different treatment groups of Babesia microti with expressed pentose phosphate pathway-related, DNA replication-related, antioxidation-related, glycolysis-related, and glutathione-related genes were not as sensitive to artemether as Plasmodium yoelii 17XNL. In particular, pentose phosphate pathway-related, DNA replication-related, and glutathione-related genes, which were actively expressed in P. yoelii 17XNL, were not actively expressed in B. microti. Supplying iron in vivo can promote the reproduction of B. microti. These results suggest that Babesia spp. lack a similar mechanism to that of malaria parasites through which the haem or iron in hemoglobin is utilized, and that this likely leads to their insensitivity to artemisinin.
Graphical Abstract