bluuebunny/crossref_metadata_2025_split huggingface dataset:
P-417 Transmyometrial embryo transfer as a reliable alternative to challenging transcervical embryo transfer
Authors: Kothari T 
Published: July 2024

Abstract

Study question
Can transmyometrial embryo transfer be a reliable alternative to challenging transcervical embryo transfer

Summary answer
In selected cases, where transcervical embryo transfer is impossible, transmyometrial embryo transfer is a suitable alternative.

What is known already
Transmyometrial embryo transfer (TMET) can be a last resort option for challenging transcervical embryo transfer (ET). Indications for TMET include; failure to access the uterus transcervically due to previous cervical surgery, stenosed cervix which will not dilate or due to challenging cervical anatomy. This technique is done by passing a long needle through the myometrium to enter the uterine cavity. This can be a less traumatic option than multiple attempts at ET with the added consequences of using a tenaculum. This centre has been performing TMET since 2004.

Study design, size, duration
This was a retrospective audit looking at TMET cases from 2004 to 2023. 125 cases were recorded and reviewed.

Participants/materials, setting, methods
The results are from a single centre unit which receives referrals for TMET from outside units. This was an audit and cases were initially found by reviewing all cases of embryo transfer from 2004. Where TMET had been recorded, the notes were then collected to ascertain patient demographics, reasons for transmyometrial embryo transfer, embryo grading and pregnancy outcomes.

Main results and the role of chance
Since 2004, 125 cases of TMET were recorded. 16 notes were excluded as there was unclear documentation on the type of embryo transfer, leaving 109 cases. There were 23 positive pregnancy tests, 6 documented scans showing a fetal heart at 7 weeks and three documented live births. Indication for TMET was mainly a failure to enter the uterine cavity due to stenosed cervix. In all cases of TMET, patient’s had undergone multiple attempts at accessing the uterine cavity, along with multiple attempts at hysteroscopy and dilatation. Only after trying all other options was TMET used, and mainly as a last resort measure. All cases were planned and used frozen blastocysts. There were no complications to TMET. Due to the last resort nature of TMET and the reasons for undergoing assisted reproductive technology it is unlikely these pregnancies were by chance.

Limitations, reasons for caution
Due to the length of time this centre has been doing TMET the documentation from the earlier cases was poor and births could have been missed due to poor follow up. Training in TMET is difficult due to the low numbers per year.

Wider implications of the findings
TMET remains a safe and reliable alternative option when facing a challenging transcervical embryo transfer and should be used as a last resort measure.

Trial registration number
not applicable
P-574 Anti-Müllerian hormone: A novel marker for ovarian torsion?
Authors: Siegler Y , Gutzeit O , Justman N , Bachar G , Wolfovitz A , Shahak G , Fainaru O 
Published: July 2024

Abstract

Study question
Can measuring plasma AMH levels assist in diagnosing ovarian torsion?

Summary answer
AMH levels show fluctuations during the acute phase of ovarian torsion, potentially aiding in clinical diagnosis.

What is known already
Anti-Müllerian Hormone (AMH), a measure of the ovarian follicular reserve, might fluctuate upon ovarian ischemia as per the “burnout theory,” where ovarian ischemia triggers primordial follicle recruitment and increased follicular growth. Accordingly, ultrasound indicators of ovarian torsion include the presence of small follicles at the ovarian periphery. Our hypothesis suggests that ovarian ischemia from torsion could alter serum AMH levels, offering diagnostic value.

Study design, size, duration
A prospective observational study was conducted in a single tertiary care center between 2021-2023. The study analyzed serum AMH levels in 17 patients aged 12-45 admitted with acute abdominal pain and undergoing diagnostic laparoscopy due to suspected ovarian torsion. Patients with AMH levels below the 5th percentile were excluded.

Participants/materials, setting, methods
Patients with suspected ovarian torsion underwent diagnostic laparoscopy based on clinical and sonographic criteria. Peripheral blood samples collected upon admission and on the first postoperative day were used to measure plasma AMH levels. AMH levels were compared between patients with confirmed ovarian torsion and those without this diagnosis.

Main results and the role of chance
Demographic characteristics were similar between the groups. Patients diagnosed with ovarian torsion showed higher pre- and postoperative AMH levels than those without torsion (4.33∓1.58 vs. 2.8∓1.28 ng/ml, p = 0.08 and 4.16∓1.52 vs. 2.71∓1.3 ng/ml, p = 0.09, respectively), but these differences were not statistically significant. However, the change in AMH levels from pre- to postoperative was more significant in patients with ovarian torsion compared to those without (0.66∓0.34 vs. 0.21∓0.18, p = 0.01).

Limitations, reasons for caution
• Small study size
• High variability in basal AMH levels in women of reproductive age

Wider implications of the findings
These results suggest that ovarian ischemia might influence AMH secretion, potentially serving as part of diagnostic evaluations. Ongoing studies aim to validate AMH as a biomarker for ovarian torsion, aiming to reduce unnecessary surgeries, lower patient risks, and minimize healthcare costs.

Trial registration number
0151-21-RMB
P-631 Extended letrozole regimen versus routine letrozole regimen in women with polycystic ovary syndrome undergoing their first ovulation induction cycle
Authors: Zhu X 
Published: July 2024

Abstract

Study question
Whether an extended letrozole regimen could result in a higher ovulatory rate than a routine regimen in PCOS women undergoing their first ovulation induction cycle.

Summary answer
PCOS women using the extended letrozole regimen failed to obtain a statistically higher rate of ovulation in comparison with the routine letrozole regimen.

What is known already
Letrozole has become the first-line agent for ovulation induction, however, nonresponsive cycles occurred in 10-58.8% of PCOS women during their ovulation induction therapy with letrozole alone. The extended letrozole regimen has been demonstrated to be a feasible method for inducing ovulation in those nonresponders. However, whether it could be applied to all the PCOS women as a first choice in the induction of ovulation remains to be explored.

Study design, size, duration
This is a prospective randomized controlled trial including 148 women with PCOS undergoing their first ovulation induction cycle with letrozole from January 2021 to October 2022.

Participants/materials, setting, methods
Participants were randomly assigned to receive an extended letrozole regimen (5 mg letrozole daily for 7 days) or a routine regimen(5 mg letrozole daily for 5 days) for one treatment cycle. Ovulation rate was the primary outcome. Secondary outcomes included the clinical pregnancy rate, the number of preovulatory follicles, the rate of multiple pregnancies.

Main results and the role of chance
The ovulation rate among women receiving a 7-day regimen was slightly higher than the rate with a 5-day regimen, but it did not reach a statistical significance in both the intention-to-treat analysis (90.54%[67/74]vs. 82.43%[59/74], P = 0.065) and per-protocol analysis (90.54%[67/74]vs. 84.29%[59/70], P = 0.257). The number of preovulatory follicles was nearly identical in the two groups (1.39±0.62 vs.1.37±0.59, P = 0.956), and no cases of ovarian hyperstimulation syndrome were observed. In the per-protocol analysis, the rates of clinical pregnancy (20.27%[15/74]vs.16.95%[10/70], P = 0.343) and live birth (13.51%[10/74]vs.11.43%[8/70], P = 0.976) did not differ significantly between treatment groups. Moreover, all the conceptions were singletons without neonatal defects.

Limitations, reasons for caution
The major concern of the current research is its single-centre and open label nature. Additionally, the limited number of lean PCOS women with a mean body mass index of 23-25 kg/m2 enrolled in our trial also restrict the generalizability of our findings.

Wider implications of the findings
Letrozole 5-day regimen remains to be the first choice for PCOS women undergoing ovulation induction therapy. Additional prospective trials with a larger sample size and different subgroups of PCOS are needed to assess the ovulatory effects of different letrozole treatment duration.

Trial registration number
ChiCTR2100042082
P-665 High FSH level impairs VEGF secretion by thawed human ovarian tissue
Authors: Einenkel R , Schallmoser A , Sänger N 
Published: July 2024

Abstract

Study question
How does a high FSH level as related to POI (premature ovarian insufficiency) affect VEGF secretion by thawed human ovarian tissue?

Summary answer
After thawing, the high FSH concentration of 175mIU/mL (10ng/mL) significantly decreased VEGF secretion by human ovarian tissue by 25.6%. 17.5mIU/mL did not change VEGF secretion.

What is known already
Cryopreservation of ovarian cortical tissue has become an important method in fertility preservation. However, 70% of the follicles do not survive the reimplantation process due to an insufficient blood supply and oxidative stress.
Human ovarian tissue secretes angiogenic factors, including VEGF, spontaneously. Its regulation by FSH is not known although 50% of the reimplantation patients show increased FSH levels (&gt;25mIU/mL) due to POI.

Study design, size, duration
Provided a signed consent, biopsy punches of ovarian cortical tissue from 8 patients undergoing fertility preservation were studied. Slow freezing and thawing was applied as in the intern routine instructions.

Participants/materials, setting, methods
Human ovarian cortical tissue was cultured in full medium at 37 °C for 48h after thawing in presence or absence of 17.5mIU/mL (1ng/mL) or 175mIU/mL (10ng/mL) recombinant human FSH. VEGF-A secretion was measured by ELISA. The expression of VEGF-A, HIF-1α and FSHR was assessed by immunohistofluorescence per follicle. The effect of FSH was assessed by one-way-ANOVA with Tukey’s post test. The effect of culture or follicular maturation stage was analyzed by t test.

Main results and the role of chance
After thawing, VEGF secretion recovers and rises over time. The addition of 175mIU/mL FSH significantly impaired VEGF-A expression compared to untreated ovarian tissue (p = 0.016). The analysis of 481 follicles showed similar results of FSH affecting VEGF-A expression by immunostaining. In particular, primordial follicles expressed significantly less VEGF-A compared to growing follicles (primary+secondary; p &lt; 0.0001). 48h tissue culture significantly increased VEGF-A expression in primordial follicles (p = 0.0041). The addition of the high FSH level significantly decreased VEGF-A expression in growing follicles (p = 0.0005).

Limitations, reasons for caution
Although VEGF-A is a key factor in angiogenesis, more factors are known to affect angiogenesis. The direct effect on angiogenesis should be evaluated. Moreover, the conditions in tissue culture may not represent those after reimplantation.

Wider implications of the findings
High FSH levels, as seen in patients with POI, might impair ovarian VEGF expression and angiogenesis. Hormone replacement therapy (HRT) might be endorsed before and during ovarian tissue reimplantation. More clinical and biological data are required to understand the regulators of angiogenesis after ovarian tissue reimplantation adequately.

Trial registration number
not applicable
P-667 The RANK-RANKL-OPG System - A new player in Oocyte Maturation
Authors: Yerushalmi G  M , Yung Y , Bakish T , Orvieto R , Hourvitz A 
Published: July 2024

Abstract

Study question
Does the RANK-RANKL-OPG system play a role in oocyte maturation and ovulation?

Summary answer
RANKL, a new ovulatory gene expressed by cumulus and mural granulosa cells activates RANK receptors in oocytes, promoting oocyte maturation through oocyte-granulosa cell communication.

What is known already
The receptor activator of nuclear factor-kB (RANK), its ligand RANKL, and the soluble decoy osteoprotegerin (OPG) system are known due to their role in bone biology, the immune system, and other tissues. It was recently shown that RANKL was a highly upregulated gene in our ovulation-associated gene library of cumulus cells (CCs) from mature and non-mature oocytes. However, its ligand, RANK was undetected in both samples. The goal of this study was to elucidate the expression and function of the RANK-RANKL-OPG system in the ovary during the preovulatory period, and ovulation.

Study design, size, duration
In vitro and in vivo experiments using mice and human oocytes and granulosa cells.

Participants/materials, setting, methods
RANKL regulation experiments involve granulosa cells isolated from follicular fluid as well as mice oocytes. Analysis included cell culture, qPCR, and western blot. To examine RANK-RANKL-OPG function upon ovulation and oocyte maturation, super-ovulated mice and human oocytes were used.

Main results and the role of chance
We demonstrated for the first time that RANK mRNA is expressed in murine oocytes. Moreover, RANKL expression was demonstrated in human MGCs and CCs and is regulated by hCG/LH and PGE2. The addition of RANKL peptide, to the murine and human oocyte during IVM procedure, induces the maturation of GV oocytes. OPG (natural RANKL inhibitor) injection to mice during super-ovulation reduced oocyte maturation rate.

Limitations, reasons for caution
Animal model results may not fully translate to humans. Additional studies are needed to confirm the effects of RANKL/RANK-OPG system on fertility and long-term health.

Wider implications of the findings
Our observations suggest that RANKL expressed by granulosa cells acts on the RANK receptor found in the oocyte and plays an important role in oocyte-granulosa cell communication activating oocyte maturation. This research contributes to new insights in understanding pre-ovulatory processes and may improve the procedure of in vitro maturation (IVM).

Trial registration number
not applicable
Sharks Violate Rensch's Rule for Sexual Size Dimorphism
Authors: Gayford J H , Sternes P C 
Published: July 2024

Synopsis
Systematic trends in body size variation exist in a multitude of vertebrate radiations, however their underlying ecological and evolutionary causes remain poorly understood. Rensch's rule describes one such trend—in which the scaling of sexual size dimorphism (SSD) depends on which sex is larger. Where SSD is male-biased, SSD should scale hyperallometrically, as opposed to hypoallometrically where SSD is female-biased. The evidence for Rensch's rule is mixed, and comes from a small subset of total vertebrate diversity. We conducted the first empirical test of Rensch's rule in sharks, seeking to confirm or refute a long-hypothesied trend. We find that sharks violate Rensch's rule, as the magnitude of SSD increases with body size despite sharks predominantly exhibiting female-biased SSD. This adds to a growing literature of vertebrate clades that appear not to follow Rensch's rule, suggesting the absence of a single, conserved scaling trend for SSD amongst vertebrates. It is likely that selection associated with fecundity results in the “inverse Rensch's rule” observed in sharks, although additional studies will be required to fully reveal the factors underlying SSD variation in this clade.
Reputations and Change in International Relations
Authors: Baser Ekrem T 
Published: July 2024

Abstract
Reputations for resolve are critical in international relations for deterring adversaries and reassuring partners. However, a state’s resolve is unobservable and can change unbeknownst to its audience. How does the possibility of unobserved change impact reputation dynamics? I provide a theory of long-run reputations with changing resolve via a formal model covering conflict and cooperation domains. In the model, the possibility that current reputations are based on outdated information makes the audience extend the benefit of the doubt to states with poor reputations. This leads to states building or spending their reputations depending on their current reputations. Importantly, when damaged reputations can be rebuilt, states with better reputations face stronger temptations to spend them. Thus, reputations constrain states with poor reputations the most. Further, because demonstrations of resolve improve reputations, which, in turn, reduce incentives for future demonstrations of resolve, there is a cyclical rhythm to conflict and cooperation. A major implication is that a state’s behavior changes with its reputation even if its resolve is unchanged and the stakes are identical. Reputational enforcement works, but the price is occasional breaches of trust. These results also settle a few long-standing controversies in the IR-reputation literature.
Systematic in vitro optimization of antimicrobial peptides against Escherichia coli
Authors: Shukri Ali , Carroll Amanda C , Collins Ryan , Charih Francois , Wong Alex , Biggar Kyle K 
Published: July 2024

Abstract

Objectives
Antimicrobial resistance is a growing concern and claims over 1 million lives per year. The discovery of new antimicrobial drugs is expensive and often generates low profitability, with very low success rates. One way to combat this is by the improvement of known antimicrobials, such as antimicrobial peptides (AMPs). The aim of this study was to improve the antimicrobial activities of two known AMPs, UyCT3 and indolicidin, with the use of peptide libraries and growth curves.

Methods
Peptide permutation libraries were synthesized for two AMPs, indolicidin and UyCT3, which included 520 peptides. These peptides were subsequently tested against MG1655-K12, to which subsequent peptide design was performed, then tested against three clinically Gram-negative relevant drug-resistant isolates. Best-performing candidates were subjected to a haemolysis assay for toxicity validation.

Results
Single amino acid permutations of UyCT3 and indolicidin were sufficient to inhibit growth of MG1655-K12, and subsequent generations of peptide design were able to inhibit growth of clinical isolates at concentrations as low as 5 µM. Our best-performing AMP, UyCT3I5A, W6Y, K10I, F13I, was not seen to be toxic towards sheep RBCs.

Conclusions
The efficacy of the AMPs improved with the use of our peptide library technology, whereby an AMP was found that inhibited bacterial growth of clinical Gram-negative isolates 4-fold better than its WT counterpart.
A postmortem case report involving fentanyl, desalkylgidazepam, and bromazolam
Authors: Ballotari Marco , Truver Michael T , Dhoble Leena R , Kinsey Amy M , Hoyer Jennifer L , Chronister Chris W , Goldberger Bruce A 
Published: July 2024

Abstract
The emergence of new psychoactive substances (NPS) and the number of new chemically diverse substances in the global illicit drug market have significantly increased over the last few years. Designer benzodiazepines are some of the most misused NPS worldwide, contributing to both nonfatal and fatal drug overdose cases. The use of desalkylgidazepam and bromazolam has recently emerged, and their prevalence has been internationally reported. In this study, we quantified desalkylgidazepam and bromazolam using gas chromatography coupled with mass spectrometry (GC–MS) in the postmortem specimens of a subject found deceased due to suspected drug overdose. A 24-year-old white male with a history of drug use was found unresponsive and not breathing in his home with drug paraphernalia nearby. A yellow powdery substance and prescription tablets were also found at the scene. The GC–MS analysis of the postmortem blood and urine samples confirmed the presence of fentanyl, desalkylgidazepam, and bromazolam. The desalkylgidazepam concentration was 1100 ng/mL in the blood, which was higher than previous reports in the literature, and estimated to be 89 ng/mL in the urine. The bromazolam concentration was 352 ng/mL in the blood and estimated to be 398 ng/mL in the urine. Additionally, fentanyl was detected in the blood (11 ng/mL), and fentanyl, norfentanyl, and gabapentin were detected in the urine. The present study aims to provide the toxicological community with information regarding a fit-for-purpose analysis of two NPS benzodiazepines.
Total third-degree variation for noise reduction in atomic-resolution STEM images
Authors: Kawahara Kazuaki , Ishikawa Ryo , Sasano Shun , Shibata Naoya , Ikuhara Yuichi 
Published: July 2024

Abstract
Scanning Transmission Electron Microscopy (STEM) enables direct determination of atomic arrangements in materials and devices. However, materials such as battery components are weak for electron beam irradiation, and low electron doses are required to prevent beam-induced damages. Noise removal is thus essential for precise structural analysis of electron-beam-sensitive materials at atomic resolution. Total square variation (TSV) regularization is an algorithm that exhibits high noise removal performance. However, the use of the TSV regularization term leads to significant image blurring and intensity reduction. To address these problems, we here propose a new approach adopting L2 norm regularization based on higher-order total variation. An atomic-resolution STEM image can be approximated as a set of smooth curves represented by quadratic functions. Since the third-degree derivative of any quadratic function is 0, total third-degree variation (TTDV) is suitable for a regularization term. The application of TTDV for denoising the atomic-resolution STEM image of CaF2 observed along the [001] zone axis is shown, where we can clearly see the Ca and F atomic columns without compromising image quality.
Chronic pancreatitis of jejunal ectopic pancreas: a rare cause of chronic abdominal pain
Authors: Smith Sonya Ann , Savage Jack , Roetger Nicholas , Moar Xavier 
Published: July 2024

Abstract
Ectopic pancreas (EP) is an uncommon, congenital focus of pancreatic tissue that is discontinuous with the principal pancreas. A 62-year-old female underwent multiple investigations for chronic epigastric pain. EP was identified intra-operatively. On retrospection, earlier imaging showed a thickened segment of jejunum with inflammation of the surrounding small bowel mesentery, suggestive of jejunal EP pancreatitis. Histology confirmed ectopic pancreatic tissue, with sections of the EP showing evidence of previous acute and chronic pancreatitis. When no cause for chronic abdominal pain is found, diagnostic laparoscopy should be considered, and the small bowel inspected, to further investigate for rare causes of abdominal pain, such as EP.
TeV afterglow from GRB 221009A: photohadronic origin?
Authors: Sahu Sarira , Medina-Carrillo B , Páez-Sánchez D I , Sánchez-Colón G , Rajpoot Subhash 
Published: July 2024

ABSTRACT
Gamma-ray burst (GRB), GRB 221009A, a long-duration GRB, was observed simultaneously by the Water Cherenkov Detector Array (WCDA) and the Kilometer Squared Array (KM2A) of the Large High Altitude Air Shower Observatory (LHAASO) during the prompt emission and the afterglow periods. Characteristic multi-TeV photons up to 13 TeV were observed in the afterglow phase. The observed very high-energy (VHE) gamma-ray spectra by WCDA and KM2A during different time intervals and in different energy ranges can be explained very well in the context of the photohadronic model with the inclusion of extragalactic background light models. In the photohadronic scenario, interaction of high-energy protons with the synchrotron self-Compton (SSC) photons in the forward shock region of the jet is assumed to be the source of these VHE photons. The observed VHE spectra from the afterglow of GRB 221009A are similar to the VHE gamma-ray spectra observed from the temporary extreme high-energy peaked BL Lac (EHBL), 1ES 2344+514 only during the 11th and the 12th of August, 2016. Such spectra are new and have been observed for the first time in a GRB.