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Introduction: High-dose therapy with melphalan followed by autologous stem cell transplant in the upfront setting (upfront ASCT) has significantly improved clinical outcomes of myeloma patients and become the standard of care for the past 30 years. However, with the advent of modern induction therapy, the role of upfront ASCT approach has been called into question. Several prospective studies have examined whether continuing with triplet therapy as consolidation with optional ASCT at relapse (triplet-alone) could result in comparable outcomes. Methods: This was a systematic review and meta-analysis of randomized controlled trials comparing upfront ASCT versus triplet-alone approach among myeloma patients treated with triplet therapy, which included two novel agents and a corticosteroid, as induction. Cochrane Library, PubMed and conference proceedings were searched. Primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), safety, and second primary malignancies (SPM). Subgroup analysis was conducted for high-risk cytogenetics. Results: Our search yielded three trials, conducted between 2010–2018, including 1,737 patients. Two trials evaluated bortezomib plus lenalidomide (VRd) induction and the third study tested carfilzomib plus lenalidomide (KRd) induction. Maintenance was given in all trials to both arms. There was no difference in OS between the arms; the pooled OS in all patients and those with high-risk cytogenetics was hazard ratio (HR) 1.03 (95% CI, 0.85–1.26; I2 = 0%; 1,737 patients, 3 trials) and 0.85 (95% CI, 0.59–1.23; I2 = 0%; 222 patients, 2 trials), respectively. The pooled PFS for upfront ASCT versus triplet-alone was significantly improved in all the patients and in the high-risk cytogenetics subgroup, HR 0.67 (95% CI 0.59–0.76; I2 = 0%; 1,737 patients, 3 trials) and HR 0.59 (95% CI: 0.44–0.7; I2 = 0%; 306 patients, 3 trials), respectively. The risk of any grade 3–4 adverse events was higher in the upfront ASCT arm versus triplet-alone approach (relative risk = 1.17 [95% CI, 1.12–1.23; 1,737 patients]). The risk of secondary malignancies was reported in all three trials and was comparable between both arms. Two trials reported on secondary myeloid neoplasms, which were significantly higher among upfront ASCT arm versus triplet-alone approach, OR 9.7 (1.8–52.25, I2 = 0%, 1,422 patients). Conclusion: Although upfront ASCT approach, in the era of triplet therapy, resulted in a significantly longer PFS among all patients, this did not translate into a survival benefit, regardless of cytogenetic risk. Upfront ASCT was associated with an increased rate of secondary myeloid neoplasms. In the current plethora of innovative therapies, the role of upfront ASCT is debatable. [ABSTRACT FROM AUTHOR]

Multiple pregnancies are infrequently encountered, with the incidence of spontaneous triplet pregnancies estimated at approximately 1 in 7000 pregnancies. Triplet gestations are recognized for their propensity to bring about a spectrum of pregnancy related complexities, encompassing fetal structural abnormalities, neurological anomalies, disturbances in amniotic fluid levels, preterm labor, and suboptimal neonatal outcomes. Anencephaly is a serious congenital defect where the brain and skull do not fully develop, often leading to a poor prognosis. It's a preventable neural tube defect (NTD) with timely intake of folic acid, is caused by the incomplete closure of the neural tube during fetal development, resulting in the absence of the cerebrum (responsible for thinking and coordination) and the front part of the brain (forebrain) in affected infants. While anencephaly in a triplet is scarcely reported, spontaneous reabsorption of an anencephalic fetus in utero is a rare and unexpected event, with no documented cases in triplet pregnancies until now. We report a case of anencephaly in a triplet pregnancy where the mother presented late during her third trimester, the reabsorption of the anencephalic fetus in utero is an unprecedented event, highlighting the unique nature of this triplet pregnancy.

This study examined the suckling behaviour of triplet-rearing ewes for three days post-parturition. Twenty-six ewes were enrolled with 11 being observed for the entire 3-days post-lambing. The behaviour of the ewe, number of lambs present at the end of the event and the behaviour that terminated the event were recorded for each suckling event. The mean suckling event duration increased when additional lambs were present at the end of the suckling event. Ewes that had observations across all three days showed no change in the number of suckling events over time, but suckling events tended to be shorter on day 3 than on days 1 or 2. On day 1 more suckling events were terminated by the ewe walking away from her lambs than on days 2 and 3. The odds of a ewe walking away to terminate the suckling event were greater when three lambs were present compared with two. Ewes showed more inactive behaviours when more lambs were present at the end of the suckling event. The results partially supported the hypothesis that the ewe would be more likely to terminate a suckling event when three lambs were attempting to suck compared with one or two lambs. [ABSTRACT FROM AUTHOR]

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Abstract Aim To conduct a comparative analysis of risk factors for retinopathy of prematurity (ROP) in single- and multiple-born neonates. Methods In a retrospective evaluation of 521 premature neonates, encompassing singletons, twins, and triplets born at or before 34 weeks of gestational age with a birthweight of less than 2000 g and who completed the ROP screening program, between 2020 and 2023, in outpatient referral ROP screening clinic affiliated by Shiraz University of Medical Sciences, were included. Neonates with the eligibility criteria were enrolled in the screening program from 28 days old age and followed up to discharge or treatment based on national ROP screening guideline. Data on ROP severity, outcome, treatment modality, and risk factors, including gestational age (GA), birth weight (BW), sex, duration of neonatal intensive care unit (NICU) admission, oxygen supplementation, mechanical ventilation, blood transfusion, method of delivery, and maternal and neonatal comorbidities, were extracted and compared between premature neonates from singleton and multiple births. Results The analysis of the ROP severity distribution revealed 238 neonates (45.7%) with low-risk (type 2 prethreshold ROP or less severe) ROP and 16 (3.1%) with high-risk (type I prethreshold ROP or more severe) ROP who underwent treatment. According to the comparative analysis of risk factors in neonates with ROP requiring treatment, multiple birth neonates exhibited significantly greater GA (27.50 ± 3.27 vs. 30.00 ± 2.00 vs. 31.14 ± 0.38 weeks, p = 0.032 for singletons, twins and triplets, respectively); greater BW (861.67 ± 274.62 vs. 1233.33 ± 347.75 vs. 1537.14 ± 208.86 g, p = 0.002); and shorter duration of NICU admission (60.17 ± 21.36 vs. 34.00 ± 12.17 vs. 12.00 ± 6.32 days, p = 0.001) and oxygen supplementation (47.33 ± 16.57 vs. 36.00 ± 8.49 vs. 4.60 ± 2.41 days, p = 0.001). There was no significant difference between single-born neonates and multiple-born neonates regarding the prevalence of other risk factors. Multiple-born neonates with no ROP and low risk ROP showed significantly lower GA and BW compared to singletons (p

This communication depicts about the successful treatment of the dystocia due to triplets in a goat. [ABSTRACT FROM AUTHOR]

Aim: To conduct a comparative analysis of risk factors for retinopathy of prematurity (ROP) in single- and multiple-born neonates. Methods: In a retrospective evaluation of 521 premature neonates, encompassing singletons, twins, and triplets born at or before 34 weeks of gestational age with a birthweight of less than 2000 g and who completed the ROP screening program, between 2020 and 2023, in outpatient referral ROP screening clinic affiliated by Shiraz University of Medical Sciences, were included. Neonates with the eligibility criteria were enrolled in the screening program from 28 days old age and followed up to discharge or treatment based on national ROP screening guideline. Data on ROP severity, outcome, treatment modality, and risk factors, including gestational age (GA), birth weight (BW), sex, duration of neonatal intensive care unit (NICU) admission, oxygen supplementation, mechanical ventilation, blood transfusion, method of delivery, and maternal and neonatal comorbidities, were extracted and compared between premature neonates from singleton and multiple births. Results : The analysis of the ROP severity distribution revealed 238 neonates (45.7%) with low-risk (type 2 prethreshold ROP or less severe) ROP and 16 (3.1%) with high-risk (type I prethreshold ROP or more severe) ROP who underwent treatment. According to the comparative analysis of risk factors in neonates with ROP requiring treatment, multiple birth neonates exhibited significantly greater GA (27.50 ± 3.27 vs. 30.00 ± 2.00 vs. 31.14 ± 0.38 weeks, p = 0.032 for singletons, twins and triplets, respectively); greater BW (861.67 ± 274.62 vs. 1233.33 ± 347.75 vs. 1537.14 ± 208.86 g, p = 0.002); and shorter duration of NICU admission (60.17 ± 21.36 vs. 34.00 ± 12.17 vs. 12.00 ± 6.32 days, p = 0.001) and oxygen supplementation (47.33 ± 16.57 vs. 36.00 ± 8.49 vs. 4.60 ± 2.41 days, p = 0.001). There was no significant difference between single-born neonates and multiple-born neonates regarding the prevalence of other risk factors. Multiple-born neonates with no ROP and low risk ROP showed significantly lower GA and BW compared to singletons (p < 0.001). Conclusion: Multiple gestation neonates may develop high-risk ROP requiring treatment at a greater gestational age and birth weight and at a lower duration of oxygen supplementation and NICU admission compared to the single birth neonates. This pattern prompts a reevaluation of screening criteria, suggesting a potential need to consider multiple birth neonates with lower traditional risk factors in screening programs. This pattern should be further evaluated in larger populations of multiple born premature neonates. [ABSTRACT FROM AUTHOR]

Background: The condition of monozygotic, monochorionic triplet fetuses with a pair of conjoined twins is extremely rare (close to one in a million births), presents challenges in its management, and with poor prognosis. Case report: We report a case of monochorionic diamniotic triplet pregnancy, ultrasound at 14 weeks shows a pair of conjoined thoracopagus fetuses, sharing heart, liver, and umbilical cord, in addition to omphalocele. The third fetus, without malformations, presents signs of early heart failure compatible with twin‐to‐twin transfusion syndrome. It was decided to carry out expectant management where at 18 weeks, intrauterine death of the three fetuses occurs. An abortion is performed by hysterotomy. Conclusions: The treatment in these cases is discussed, three management options have been proposed: expectant management, selective reduction of the conjoined fetuses, or termination of the pregnancy. A review of the literature found only 12 cases with this combination of pathologies, in which only 3 normal fetuses (25%) survived and none of the conjoined twins survived. To our knowledge, this case is the first of a monochorionic triplet pregnancy with conjoined fetuses complicated with early twin‐to‐twin transfusion. [ABSTRACT FROM AUTHOR]

Understanding the host‐guest interactions for thermally activated delayed fluorescence (TADF) emitters is critical because the interactions between the host matrices and TADF emitters enable precise control on the optoelectronic performance, whereas technologically manipulating the singlet and triplet excitons by using different kinds of host‐guest interactions remains elusive. Here, we report a comprehensive picture that rationalizes host‐guest interaction‐modulated exciton recombination by using time‐resolved spectroscopy. We found that the early‐time relaxation is accelerated in polar polymer because dipole‐dipole interaction facilitates the stabilization of the 1CT state. However, an opposite trend is observed in longer delay time, and faster decay in the less polar polymer is ascribed to the π‐π interaction that plays the dominant role in the later stage of the excited state. Our findings highlight the technological engineering singlet and triplet excitons using different kinds of host‐guest interactions based on their electronic characteristics. [ABSTRACT FROM AUTHOR]

The yolov5-CTD (you only look once version five-carafe triplet double attention vision transformer) coil defect detection algorithm is proposed to address the problems associated with the manufacturing process of wireless charging coils, which are the core component of wireless chargers and can produce multiple types of defects. To address the problem of small area defects, a large amount of detail semantic information is lost in the process of down-sampling in the backbone network. DA-ViT (Double Attention Vision transformer) is incorporated into the enhanced feature extraction network to supplement the detail semantic information and enhance the ability of the network to build up the extraction of long-distance information. The Triplet attention mechanism module is introduced to be embedded in the lateral hop connection of the multiscale feature extraction network to enhance the neck network's ability for local information extraction by rotating the dimension for multidimensional feature capture and improve the effect of multiscale feature fusion. For the large number of extreme aspect ratio defects in the coil, Carafe up sampling is used to aggregate contextual information to improve the perceptual field, while optimising the jaggedness and mosaic phenomenon of the defect edges of the feature map caused by nearest neighbor interpolation up sampling. To enable the backbone feature extraction network to learn better feature information, the convolution part of yolov5 is optimised to dynamic conditional convolution. Experiments have shown that yolov5-CTD can detect surface defects on mobile phone wireless charging coils with the accuracy of Map@0.5 reaches 80.9% which is 4.8% higher than the original network, and the detection speed is 41.15FPS, which can meet the industrial production line requirements in terms of speed and accuracy. [ABSTRACT FROM AUTHOR]

Compared with singleton pregnancies, triplet pregnancies are associated with a significantly increased risk of adverse pregnancy outcomes. Early ultrasound examination is the best way to diagnose triplets, establish dating, and determine the number of placentas to provide appropriate counseling and monitoring. Dichorionic placentation adds risks specifically associated with a shared placenta, and limits options for intervention. Multifetal reduction is an option that can significantly improve pregnancy outcomes compared with non-reduced triplet pregnancies. Integration of a Maternal-Fetal Medicine specialist in the prenatal care for a triplet pregnancy reduces the risk of preeclampsia, preterm birth, low birthweight infants, perinatal mortality, and major neonatal morbidity. [ABSTRACT FROM AUTHOR]

The two key concerns in treating locally advanced rectal cancer (LARC) are as follows: (i) prolonging survival by reducing distant metastases and (ii) maintaining anorectal function and quality of life in surviving patients by safely avoiding rectal resection. To resolve these issues, in recent years, total neoadjuvant therapy (TNT), a preoperative combination of chemoradiotherapy or short-course radiotherapy (SCRT) and systemic chemotherapy, has been developed as a multidisciplinary treatment of LARC. There have been no prospective studies on consolidation triplet versus doublet regimens after SCRT. This randomized phase III trial (the ENSEMBLE trial) aims to test the superiority of consolidation irinotecan, capecitabine, and oxaliplatin over capecitabine and oxaliplatin after SCRT as TNT for LARC. The primary endpoint will be organ preservation-adapted disease-free survival in the intention-to-treat population. Moreover, no predictive biomarkers have been established for LARC. Therefore, to explore the predictive biomarkers for estimating the response to TNT and non-operative management, we planned translational research using multi-omics data, including genomic profiling with whole-genome/transcriptome sequencing of tissue and blood samples, liquid biopsy, radiomics, digital pathology, clinical features by deep learning with artificial intelligence.

Abstract Understanding the host‐guest interactions for thermally activated delayed fluorescence (TADF) emitters is critical because the interactions between the host matrices and TADF emitters enable precise control on the optoelectronic performance, whereas technologically manipulating the singlet and triplet excitons by using different kinds of host‐guest interactions remains elusive. Here, we report a comprehensive picture that rationalizes host‐guest interaction‐modulated exciton recombination by using time‐resolved spectroscopy. We found that the early‐time relaxation is accelerated in polar polymer because dipole‐dipole interaction facilitates the stabilization of the 1CT state. However, an opposite trend is observed in longer delay time, and faster decay in the less polar polymer is ascribed to the π‐π interaction that plays the dominant role in the later stage of the excited state. Our findings highlight the technological engineering singlet and triplet excitons using different kinds of host‐guest interactions based on their electronic characteristics.

A fused triplet placenta was observed in a Wistar Hannover rat on gestation day 15. Each placenta (referred to as PL-A, PLB, and PL-C) of this fused placenta was attached to one fetus each, but their fetal weights were lower than that of the fetus attached to the only normal placenta (referred to as PL-N) in this dam. Histopathologically, thinning of the trophoblastic septa and dilatation of the maternal sinusoid in the labyrinth zone were observed in PL-B and PL-C, but not in PL-A or PL-N. The points of placental fusion were at the junctional zone derived from each side of the placenta without connective tissues, and the septum was composed of trophoblastic giant cells. Although PL-A had a solitary metrial gland, PL-B and PL-C shared one metrial gland with one spiral artery terminus branching towards each labyrinth zone. [ABSTRACT FROM AUTHOR]

Objective: Monochorionic (MC) triplet pregnancies are extremely rare and information on these pregnancies and their complications is limited. We aimed to investigate the risk of early and late pregnancy complications, perinatal outcome and the timing and methods of fetal intervention in these pregnancies. Methods: This was a multicenter retrospective cohort study of MC triamniotic (TA) triplet pregnancies managed in 21 participating centers around the world from 2007 onwards. Data on maternal age, mode of conception, diagnosis of major fetal structural anomalies or aneuploidy, gestational age (GA) at diagnosis of anomalies, twin‐to‐twin transfusion syndrome (TTTS), twin anemia–polycythemia sequence (TAPS), twin reversed arterial perfusion (TRAP) sequence and or selective fetal growth restriction (sFGR) were retrieved from patient records. Data on antenatal interventions were collected, including data on selective fetal reduction (three to two or three to one), laser surgery and any other active fetal intervention (including amniodrainage). Data on perinatal outcome were collected, including numbers of live birth, intrauterine demise, neonatal death, perinatal death and termination of fetus or pregnancy (TOP). Neonatal data such as GA at birth, birth weight, admission to neonatal intensive care unit and neonatal morbidity were also collected. Perinatal outcomes were assessed according to whether the pregnancy was managed expectantly or underwent fetal intervention. Results: Of an initial cohort of 174 MCTA triplet pregnancies, 11 underwent early TOP, three had an early miscarriage, six were lost to follow‐up and one was ongoing at the time of writing. Thus, the study cohort included 153 pregnancies, of which the majority (92.8%) were managed expectantly. The incidence of pregnancy affected by one or more fetal structural abnormality was 13.7% (21/153) and that of TRAP sequence was 5.2% (8/153). The most common antenatal complication related to chorionicity was TTTS, which affected just over one quarter (27.6%; 42/152, after removing a pregnancy with TOP < 24 weeks for fetal anomalies) of the pregnancies, followed by sFGR (16.4%; 25/152), while TAPS (spontaneous or post TTTS with or without laser treatment) occurred in only 4.6% (7/152) of pregnancies. No monochorionicity‐related antenatal complication was recorded in 49.3% (75/152) of pregnancies. Survival was apparently associated largely with the development of these complications: there was at least one survivor beyond the neonatal period in 85.1% (57/67) of pregnancies without antenatal complications, in 100% (25/25) of those complicated by sFGR and in 47.6% (20/42) of those complicated by TTTS. The overall rate of preterm birth prior to 28 weeks was 14.5% (18/124) and that prior to 32 weeks' gestation was 49.2% (61/124). Conclusion: Monochorionicity‐related complications, which can impact adversely perinatal outcome, occur in almost half of MCTA triplet pregnancies, creating a challenge with regard to counseling, surveillance and management. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

In this investigation, we have been compared and contrasted the substituent effects on stability using ΔΕs‐t (Et − Es), frequency, ΔΕHOMO‐LUMO (ELUMO − EHOMO), polarity, polarizability, Mülliken charge distribution and reactivity descriptors of the singlet and triplet Hammick silylenes derived from silapyridine‐4‐ylidene (1‐s, 2x‐s, 3x‐s and 1‐t, 2x‐t, 3x‐t; x = NH, PH, AsH, O, S, and Se) as well as the synthesized dialkylsilylenes by West (4‐s), Denk (5‐s), and Kira (6‐s). In all cases, singlet (s) silylenes appear as ground states, exhibiting more stability than their corresponding triplet (t) states. All the above s and t silylenes appear as minima on their energy surfaces showing the positive force constant and the positive harmonic vibration frequency. Regardless of how orchestrated substituent groups in either "W" or "chair" position; the most stability is demonstrated by substitution of NH, and O groups in the fused pyrrole ring, while the least stability is considered by Kira's silylene. In contrast to previous report on the N‐Heterocyclic Hammick carbenes, silylenes, and germylenes (NHCs, NHSis, and NHGes) that size, type, orientation, and the number of fused rings pronounced effect on stability of the corresponding divalent species, here σ‐donor/π‐donor groups (such as PH, AsH, S, and Se) similar to σ‐acceptor/π‐donor groups (such as NH and O) stabilize their corresponding silylenes. Furthermore, the scrutinized singlet silylenes reveal lesser nucleophilicity (N), greater electrophilicity (ω), higher chemical potential (μ), higher global hardness (η), and lower global softness (S) than the analogous triplet silylenes. All singlet and triplet species show the maximum electronic charge (ΔNmax) with positive sign. [ABSTRACT FROM AUTHOR]

During this study, six carbenes, consisted of various substitutions (hydrogen, deuterium, fluorine, chlorine, bromine, and methyl) and their 24 related carbenoids (using Li, Na, Be, and Mg metals) were designed. These species were theoretically studied to obtain the extensive and comprehensive information about their structures, stabilities, atomic specifications, and bonding properties using MP2/aug-cc-pVTZ level of theory. Moreover, the PBE1PBE DFT method was used for IQA analyses using AIMAll program package. The calculated molecular parameters showed that the electronegativity and the size of ligand are effective on the studied structures. Moreover, the electronegativity effect is more important than the size. Atomic hybridizations results showed the p indexes of carbon in triplet carbenes are also smaller than those in singlet carbenes, but this difference in halogen-containing carbenes is smaller than the other carbenes. In population analyses, except for sodium-based carbenoids, all carbenoids have higher Eg values than the carbenes. The ΔG values for α-elimination reaction, as a method of preparation of these carbenes, were obtained in order of f < c < b < m < h, which is reversely related to the electronegativities of the connected ligands. IQA analyses were performed to evaluate the relative stability of carbenes. It was found that the classical interaction in C–F is attractive (negative) unlike the other mentioned bonds energy for carbenes. This electrostatic term in C–F is larger in the singlet state than the triplet state, which leads to the singlet state of CF2 being more stable and consequently more favorable than its triplet state. [ABSTRACT FROM AUTHOR]

Simple Summary: Body condition score (BCS) is an assessment of the amount of fat and muscle covering the lumbar spine and short ribs of sheep. It is widely used as a management tool to assess the nutritional status of sheep. This study investigated whether managing triplet-bearing ewes at a higher or lower BCS between pregnancy scanning and lamb marking impacted the survival of the ewes or their lambs. Triplet-bearing ewes of Maternal (crossbred or composite) or Merino breed were allocated to one of two treatments at pregnancy scanning: 'High' or 'Low' BCS. The BCS of individual ewes was assessed at pregnancy scanning, pre-lambing and marking, and ewe and lamb mortality to marking, recorded for each mob. Survival of triplet-bearing Merino ewes and their lambs was greater when ewes were managed at the High BCS compared to the Low BCS. The BCS treatment had no effect on the survival of Maternal ewes or their lambs. Survival of triplet-born Merino but not Maternal lambs was greater when ewes had a greater BCS pre-lambing or gained BCS between pregnancy scanning and pre-lambing. Triplet-bearing ewes of Maternal and Merino breed that gained BCS between pregnancy scanning and pre-lambing had greater survival to marking. Producers should, therefore, manage the nutrition of triplet-bearing Merino ewes so that ewes are in greater BCS at lambing and/or to gain BCS between pregnancy scanning and lambing to improve ewe and lamb survival. Triplet-bearing Maternal ewes should be managed to gain BCS between pregnancy scanning and lambing to improve ewe survival. This study evaluated the impacts of management of body condition score (BCS) between pregnancy scanning and lamb marking on the mortality of triplet-bearing ewes and their lambs at 19 research sites across Southern Australia. Triplet-bearing ewes of Maternal (crossbred or composite) or Merino breed were randomly allocated to treatment at pregnancy scanning at an average of 97 days from the start of joining: High or Low BCS. The BCS of individual ewes was assessed at pregnancy scanning, pre-lambing (average of 137 days from the start of joining) and marking (average of 165 days from the end of joining), and ewe and lamb mortality to marking, recorded for each mob. The average BCS at pregnancy scanning was 3.4 for Maternal ewes and 3.3 for Merino ewes. There were no breed by BCS treatment effects on the BCS of ewes at pregnancy scanning or lamb marking or on the change in BCS between pregnancy scanning and pre-lambing or between pre-lambing and marking. The change in BCS differed between the High and Low BCS treatments, between pregnancy scanning and pre-lambing (0.12 vs. −0.33; p < 0.001) and between pre-lambing and marking (−0.39 vs. 0.07; p < 0.001) but did not differ between breeds. The average BCS at marking for ewes managed at the High and Low BCS treatments was 3.1 and 3.0 for Maternals and 3.0 and 2.8 for Merinos. Survival of triplet-bearing Merino ewes (p < 0.01) and their lambs (p < 0.001) was greater when ewes were managed at the High BCS compared to the Low BCS. The BCS treatment did not impact the survival of Maternal ewes or their lambs. The survival of Merino but not Maternal lambs was higher when ewes were in greater BCS pre-lambing (p < 0.01) and when ewes gained BCS between pregnancy scanning and pre-lambing (p < 0.01). Ewe mortality was lower when ewes gained BCS between pregnancy scanning and pre-lambing (p < 0.05). Merino ewes were more likely to die than Maternal ewes for a given change in BCS between pregnancy scanning and pre-lambing (p = 0.065). Overall, our findings demonstrate that producers should manage the nutrition of triplet-bearing Merino ewes so that ewes are in greater BCS at lambing and/or to gain BCS between pregnancy scanning and lambing to improve ewe and lamb survival. Triplet-bearing Maternal ewes should be managed to gain BCS between pregnancy scanning and lambing to improve ewe survival. [ABSTRACT FROM AUTHOR]

The kinetics of triplet—triplet absorption of multiatomic molecules (by the example of halogen-substituted of fluorescein, i.e., eosin and erythrosine) is studied in the case of step population of their high triplet levels using two laser pulses with tuned delay between them. It is shown that the kinetics of the induced absorption allows estimation of the efficiency of competing relaxation channels of highly excited triplet states of molecules. In the absence of energy transfer to environment and photochemical reactions, the main relaxation channel of high triplet states of molecules containing heavy halogen atoms is the reverse triplet—singlet intersystem crossing. When interpreting the results of the study, thermal effects caused by medium heating due to nonradiative relaxation of high electronic excited states of molecules should be taken into account. [ABSTRACT FROM AUTHOR]

Simple Summary: Consultation with sheep producers in Australia revealed that understanding the impact of the number of triplet-bearing ewes in a paddock at lambing, known as the mob size, on the survival of their lambs was an important research priority. Previous research has demonstrated that smaller mob sizes at lambing improve the survival of single- and especially twin-born lambs. Therefore, we expected that lambing triplet-bearing ewes in smaller mobs would increase the survival of their lambs. Research was conducted on 12 commercial sheep farms across southern Australia between 2019 and 2021, with three farms used in two years of the experiment. Adult, triplet-bearing ewes were randomly allocated into one of two treatments, 'High' or 'Low' mob size, at about 15 days before the start of lambing. We found that lamb survival was significantly greater for lambs born in the Low compared with the High mob size treatments. Analysis of the effect of the actual mob sizes showed that reducing mob size at lambing by 10 triplet-bearing ewes increased the survival of their lambs by 1.5%. Lambing triplet-bearing ewes in smaller mobs will therefore be included in management guidelines for producers as a strategy to improve the survival of triplet-born lambs. Industry consultation in Australia revealed that the potential impact of the mob size of ewes during lambing on the survival of triplet-born lambs was an important research priority. Previous research has demonstrated that smaller mob sizes at lambing improve the survival of single- and especially twin-born lambs, regardless of ewe stocking rate. Therefore, we hypothesised that lambing triplet-bearing ewes in smaller mobs, regardless of stocking rate, will increase the survival of their lambs. Research sites were established on 12 commercial sheep farms across southern Australia between 2019 and 2021. One farm used Merinos whilst the remainder of the farms used non-Merino breeds, consisting of composite ewes joined to composite or terminal sires. Three of the farms were used in two years of the experiment. Adult, triplet-bearing ewes were randomly allocated into one of two treatments, 'High' or 'Low' mob size, at an average of 135 days from the start of joining. Ewe and lamb survival were assessed between allocation to treatments and lamb marking. Lamb survival was significantly greater for lambs born in the Low (65.6%) compared with the High (56.6%) mob size treatments (p < 0.001). There was no effect of mob size at lambing on the mortality of triplet-bearing ewes. Analysis of the effect of the actual mob sizes showed that reducing the mob size at lambing by 10 triplet-bearing ewes increased the survival of their lambs to marking by 1.5% (p < 0.001). This study has shown that the survival of triplet-born lambs can be improved by lambing triplet-bearing ewes in smaller mobs regardless of stocking rate when ranging from 0.7–13 ewes/ha. [ABSTRACT FROM AUTHOR]

Due to the fact of fascinating properties of 4-aminoantipyrene and other pyrazolone derivatives, this work is mainly focused on the synthesis of Schiff base complex of Ru-NO core containing pyrazolone as the main ligand functionality. Several spectroscopic and spectrometric techniques in association with theoretical approach (DFT) have been applied to elucidate the structure of the complex. In addition to the characterization, parameters that decide to label the given compound as a significant nitric oxide releasing molecule (NORM) have been discussed. DFT based computational studies using LANL2DZ/B3LYP and 6-31 G(d,p)/B3LYP formalism, respectively for Ru and nonmetallic atoms of the complex have been used to deal with the NO-releasing phenomenon. From the results discussed herein it is evident that the complex can release NO at the cost of low energy radiation. [ABSTRACT FROM AUTHOR]

The C--H functionalization of indole heterocycles constitutes a key strategy to leverage the synthesis of endogenous signaling molecules such as tryptamine or tryptophol. Herein, we report on the photocatalytic reaction of ethyl diazoacetate with indole, which shows an unusual solvent dependency. While C2-functionalization occurs under protic conditions, the use of aprotic solvents leads to a complete reversal of selectivity and exclusive C3-functionalization occurs. To rationalize for this unexpected reactivity switch, we have conducted detailed theoretical and experimental studies, which suggest the participation of a triplet carbene intermediate that undergoes initial C2-functionalization. A distinct cationic [1,2]-alkyl radical migration then leads to formation of C3-functionalized indole. We conclude with the application of this photocatalytic reaction to access oxidized tryptophol derivatives including gram-scale synthesis and derivatization reactions. [ABSTRACT FROM AUTHOR]

In this research, we compare and contrast the stability, polarity, polarizability, band gap, and global reactivity of singlet (s) and triplet (t) fused benzene N‐heterocyclic silylene (1‐s and 1‐t) along with five numbered congeners (2x‐s, and 2x‐t, x = CH2, SiH2, GeH2, NH, PH, AsH, O, S, and Se) at DFT (density functional theory). All singlet and triplet remote N‐heterocyclic silylenes (RNHSis) appear as minima showing positive force constant. Every singlet RNHSi emerges as ground state and exhibits more stability than its corresponding triplet RNHSi. In going from 1‐s to 2x‐s species, the thermodynamic and kinetic stability is increased, so that higher ΔEs‐t (= Et − Es) and higher band gap or ΔEHOMO–LUMO (=ELUMO − EHOMO) is considered for 2CH2‐s, 2NH‐s, and 2O‐s structures. In going from second row to forth row of every group in the periodic table, electronegativity of heteroatoms have pronounced effect on the stability, polarity, polarizability, and band gap of 2x‐s species. These silylenes show more stability than the synthesized silylene by Kira. Every 2x‐t silylene shows higher nucleophilicity (about 1.6 times) than its corresponding 2x‐s analogous. Every singlet RNHSi reveals lower nucleophilicity (N), higher electrophilicity (ω), chemical potential (μ), and global hardness (η) than its triplet congener. Furthermore, 2x‐s silylenes benefit from stabilization effect of two heteroatoms synchronously in the fused five‐membered ring via mesomeric effect and π donation from the lone pairs of heteroatom to the formally vacant 3p orbital of the silylenic center. Hence, we predict higher stability as well as lower global reactivity of RNHSis than Kira's silylene will make them creditable for the synthetic research. [ABSTRACT FROM AUTHOR]

Background. The treatment options for patients with multiple myeloma who refractory to previous bortezomib and lenalidomide therapy are limited. Pomalidomide is ап immunomodulatory agent that was registered for the treatment of patients with double refractory multiple myeloma.Aim. To evaluate efficacy, safety and optimal course of the therapy with pomalidomide in routine practice in patients with double refractory multiple myeloma.Materials and methods. Overall, 71 patients with double refractory multiple myeloma were included in the retrospective analysis. There were 36 males and 35 females. The median age was 61 years (range 35-79). According to Durie-Salmon staging system, there were 53 (79.1 %) patients in stage III, 13 (19.4 %) - stage II, and 1 (1.5 %) - stage I.The stage was unknown in 4 patients. Kidney impairment at the onset was in 10 (15 %) patients, the normal function was in 57 (85 %) patients and 4 patients had no data. Most patients (n = 68, 95.8 %) received pomalidomide in one therapy line, in 3 (4.2 %) patients - drug was given in two lines, totally 74 episodes of use. Median number of drugs prescribed prior to pomalidomide were 4 (2-9) drugs, including target ones - 2 (2-5). In the first remission 31 (43.6 %) patients received high-dose therapy with autologous stem cell transplantation. pomalidomide was administered in combination with low doses of dexamethasone (PomDex, n = 44; 59.4 %) and as a part of triple regimens (n = 30; 40.6 %). previously exposed (n = 22; 73.3 %) and new drugs (n = 8; 26.7 %) were used in the combination treatment. In 44 (61.9 %) patients pomalidomide was administered more than 3 years after the onset of the disease, median 63.5 (37-184) months. In 27 (38.1 %) patients it was given within less than 3 years after the onset, median 21 (6-36) months. The primary endpoint was progression-free survival. Secondary endpoints - pomalidomide tolerability, response rate and optimal third drug in the triple regimen. The dependence of progression-free survival, frequency of response and adverse events from the pretreatment, the choice of the third drug, gender, age, immunochemical variant, stage according to the International Staging System and to Durie-Salmon classification was studied.Results. The median time from the diagnosis to the start of pomalidomide therapy was 44.5 (6-184) months. The median of cycles with pomalidomide was 3 (1-30). The response was achieved in 52 (70 %) patients. The median progression-free survival was 4 (1-30) months, overall survival - 6 (0.5-42) months. Adverse effects were noted in 34 (46.5 %) patients. The most frequent adverse events were neutropenia grade III-IV (n = 14; 41.3 %), infection (n = 7; 20.7 %) and fatigue with limitation of daily activity (n = 6; 20.6 %). The rate of adverse events was higher in patients with triplets than doublets regimens of therapy: 43.3 % (n = 13) and 27.2 % (n = 12) respectively (p = 0.008). There were no statistically significant differences in progression-free survival between pomalidomide treatment options (two- or three-component regimen).Conclusion. Compared to the three-component therapy consisting of drugs to which refractoriness was previously diagnosed the PomDex scheme is less toxic and equally effective. Therapy with pomalidomide is effective in the majority of patients with double refractory multiple myeloma even in heavily pretreated. The toxicity is acceptable.

Spontaneous preterm birth occurs more frequently in multiple pregnancies. This syndrome has multiple triggers that result in a unified downstream pathway of cervical remodeling, uterine activity, and progressive cervical dilatation. Whilst the triggers for labor in multiple pregnancy may be different from singletons, the downstream changes will be the same. Identifying patients at risk of preterm birth is a priority as interventions to delay delivery and optimize the fetus can be initiated. Methods for screening for risk of preterm birth which focus on the detection of cervical remodeling may therefore have potential in this population. This review explores the evidence for the predictive utility for preterm birth of several published techniques that assess the physical, biomechanical, and optical properties of the cervix, with a focus on those which have been studied in multiple pregnancies and highlighting targets for future research in this population. Fifteen techniques are discussed which assess the physical, biomechanical, and optical properties of the cervix in pregnancy. Of these, only three techniques that evaluated the predictive accuracy of a technique in patients with multiple pregnancies were identified: uterocervical angle, cervical consistency index, and cervical elastography. Of these, measurement of the uterocervical angle has the strongest evidence. Several techniques have shown predictive potential in singleton pregnancies, but have not yet been studied in multiple pregnancies, which would be a logical expansion of research. Research on techniques with predictive utility for PTB in patients with multiple pregnancies is limited but should be a research priority. Overall, the theory supports the investigation of cervical remodeling as a predictor of PTB, and there are numerous techniques in development that may have potential in this field. [ABSTRACT FROM AUTHOR]

To compare the outcomes of dichorionic triamniotic (DCTA) triplets with that of monochorionic diamniotic (MCDA) twin gestations undergoing fetoscopic laser surgery (FLS) for treatment of twin-to-twin transfusion syndrome (TTTS). Retrospective cohort study of prospectively collected data of consecutive DCTA triplet and MCDA twin pregnancies with TTTS that underwent FLS at two fetal treatment centers between 2012 and 2020. Preoperative, operative and, postoperative variables were collected. Perinatal outcomes were investigated. Primary outcome was survival to birth and to neonatal period. Secondary outcomes were gestational age (GA) at birth and procedure-to-delivery interval. Literature review was conducted in which PubMed, Web of Science, and Scopus were searched from inception to September, 2020. Twenty four sets of DCTA triplets were compared to MCDA twins during the study period. There were no significant differences in survival (no survivor, single, or double survivors) to birth and to the neonatal period of the MC twin pairs of the DCTA triplets vs MCDA twins. Median GA at delivery was approximately three weeks earlier in DCTA triplets compared to MCDA twins (28.4 weeks vs 31.4 weeks, p =.035, respectively). Rates of preterm birth (PTB) less than 32 and less than 28 weeks were significantly higher in DCTA triplets compared to twins (<32 weeks: 70.8% vs 51.1%, p =.037, respectively, and <28 weeks: 37.5% vs 20.8%, p =.033, respectively). Perinatal survival including fetal and neonatal are comparable between DCTA triplets and MCDA twins. However, this might have resulted from the small sample size of the DCTA triplets. GA at delivery is earlier in triplets, which could be due to the nature of triplet gestation rather than to the laser procedure itself. [ABSTRACT FROM AUTHOR]

[Display omitted] • Nitroindoles show distinct T 1 state properties and applications. • 3HN-6NO 2 exhibits strong oxidizing, can generate radicals. • Dual reaction pathways identified in protic solvents. • Acidity and basicity critically influence 3HN-6NO 2 reactions. • Findings enhance understanding of nitroindoles in biosystems. Indoles are notable for their distinct photophysical and photochemical properties, making them useful indicators in biological systems and promising candidates for a variety of pharmaceutical applications. While some indoles exhibit room temperature phosphorescence, such a phenomenon has not been observed in nitroindoles. Typically, adding of a nitro group into aromatic compounds promotes ultrafast intersystem crossing and increases the formation quantum yield of the lowest excited triplet (T 1). Therefore, understanding the reactivity of nitroindoles′ T 1 states is imperative. This study investigated the physical properties and chemical reactivities of the T 1 state of 6-nitroindole (3HN-6NO 2) in both polar aprotic and protic solvents, using transient absorption spectroscopy. Our results demonstrate the basicity and acidity of 3HN-6NO 2 , emphasizing its potential for protonation and dissociation in mildly acidic and basic conditions, respectively. Furthermore, 3HN-6NO 2 has a high oxidizing capacity, participating in electron transfer reactions and proton-coupled electron transfer to produce radicals. Interestingly, in protic solvents like alcohols, 3HN-6NO 2 dissociates at the –NH group and forms N-H...O hydrogen-bonded complexes with the nitro group. By identifying transient absorption spectra of intermediates and quantifying kinetic reaction rate constants, we illuminate the unique properties of the T 1 state nitroindoles, enriching our understanding of their photophysical and photochemical behaviors. The results of this study have significant implications for their potential application in both biological systems and materials science. [ABSTRACT FROM AUTHOR]

Background: Accurate quantification of voluntary activation is important for understanding the extent of quadriceps dysfunction in individuals with anterior cruciate ligament reconstruction (ACLR). Voluntary activation has been quantified using both percent activation derived from the interpolated twitch technique and central activation ratio (CAR) derived from the burst superimposition technique, as well as by using different types of electrical stimulators and pulse train conditions. However, it is unclear how these parameters affect voluntary activation estimates in individuals with ACLR. This study was performed to fill this important knowledge gap in the anterior cruciate ligament literature. Methods: Quadriceps strength and voluntary activation were examined in 18 ACLR participants (12 quadriceps/patellar tendon graft, 6 hamstring tendon graft; time since ACLR: 1.06 ± 0.82 years, mean ± SD) at 90° of knee flexion using 2 stimulators (Digitimer and Grass) and pulse train conditions (3-pulse and 10-pulse). Voluntary activation was quantified by calculating both CAR and percent activation. Results: Results indicated that voluntary activation was significantly overestimated by CAR when compared with percent activation (p < 0.001). Voluntary activation estimates were not affected by pulse train conditions when using percent activation; however, 3-pulse stimuli resulted in greater overestimation than 10-pulse stimuli when using CAR (p = 0.003). Voluntary activation did not differ between stimulators (p > 0.05); however, the Digitimer evoked greater torque at rest than the Grass (p < 0.001). Conclusion: These results indicate that percent activation derived from the interpolated twitch technique provides superior estimates of voluntary activation than CAR derived from burst superimposition and is less affected by pulse train conditions or stimulators in individuals with ACLR.

A triplet diphenylcarbene, bis[3-bromo-5-(trifluoromethyl)[1,1'-biphenyl]-4-yl]methylidene (B3B), with exceptional stability was discovered by chemists from Japan's Mie University. To investigate its different quantum chemical features, a theoretical analysis was predicated on Density Functional Theory (DFT) and Time Dependent-DFT (TD-DFT) based technique. According to the findings, the singlet–triplet energy gap (ES-T), as well as HOMO–LUMO energy bandgap (EH-L), was found to be diminished when nucleophilicity (N) rose. We looked at the geometrical dimensions, molecular orbitals (MOs), electronic spectra, electrostatic potential, molecular surfaces, reactivity characteristics, and thermodynamics features of the title carbene (B3B). Its electronic spectra in different solvents were calculated using TD-DFT and Polarizable Continuum Model (PCM) framework. The estimated absorption maxima of B3B were seen between 327 and 340 nm, relying on the solvents, and were attributed to the S0 → S1 transition. Estimated fluorescence spectral peaks were found around 389 and 407 nm with the S1 and S0 transitions being identified. Its fluorescence/absorption intensities revealed a blue shift change when the solvent polarity was increased. The least exciting state has been discovered to be the π → π* charge-transfer (CT) phase. According to the Natural Bonding Orbital (NBO) exploration, ICT offers a significant role in chemical system destabilization. Furthermore, several hybrid features were used to determine the NLO (nonlinear optical) features (polarizability, first-order hyperpolarizability, and dipole moment). The calculated values suggest that B3B is a promising candidate for further research into nonlinear optical properties. [ABSTRACT FROM AUTHOR]

To reach new triplet ground state (T) silylenes, we compare and contrast acyclic silylenes with group 14 substituents (:Si(XH3)2 (X = C, Si, Ge, Sn, and Pb; 1C, 2Si, 3Ge, 4Sn, and 5Pb, respectively), at the B3LYP/6-311++G** level of theory. The results show that in going from 1C to 5Pb, the singlet-triplet energy gap (ΔES-T) and HOMO-LUMO energy gap (ΔEH-L) decrease while the nucleophilicity (N) increases. Structure 5Pb demonstrates the equal possibility of singlet and triplet ground states. Replacing one and two hydrogens with alkaline and alkaline earth metals leads to generate a new series of T silylenes with high stabilities. [ABSTRACT FROM AUTHOR]

The standard treatment for metastatic hormone-sensitive prostate cancer (mHSPC) is now a combination of androgen deprivation therapy plus an androgen receptor-targeted therapy (abiraterone, apalutamide, enzalutamide or darolutamide), with or without chemotherapy (docetaxel). The selection of suitable patients for each therapeutic approach has become a determining factor to ensure efficacy and minimize side effects. This article combines recent clinical evidence with the accumulated experience of experts in medical oncology, radiation oncology and urology, to provide a comprehensive view and therapeutic recommendations for mHSPC., (Copyright © 2024 The Authors. Published by Elsevier España, S.L.U. All rights reserved.)

Background: The QUATTRO-II trial examined the efficacy and safety of capecitabine+oxaliplatin+irinotecan (CAPOXIRI)+bevacizumab (BEV) vs. 5-fluorouracil+folinic acid+oxaliplatin+irinotecan (FOLFOXIRI)+BEV in metastatic colorectal cancer (mCRC)., Methods: In this phase II study (ClinicalTrials.gov: NCT04097444; jRCTs041190072), patients were randomized (1:1) to FOLFOXIRI+BEV or CAPOXIRI+BEV. The induction treatment in the FOLFOXIRI+BEV/CAPOXIRI+BEV arms was continued for 8/6 cycles (maximum 12/8 cycles if feasible), and the maintenance treatment was 5-fluorouracil/leucovorin+BEV or capecitabine+BEV at the investigators' discretion. The primary endpoint was progression-free survival (PFS), with the two arms deemed equivalent if the hazard ratio (HR) of the point estimate was 0.80 < HR < 1.25. Secondary endpoints were overall response rate (ORR), overall survival (OS), incidence of adverse events (AEs), and patient-reported outcomes., Findings: Overall, 51 and 52 patients were randomized to FOLFOXIRI+BEV and CAPOXIRI+BEV, respectively. The study met its primary endpoint; PFS at median follow-up of 23.7 months was 10.6 months (95% confidence interval [CI], 7.7-13.3) in the FOLFOXIRI+BEV arm vs. 10.9 months (95% CI, 9.3-14.3) in the CAPOXIRI+BEV arm (HR 1.114 [0.80 < HR < 1.25], p = 0.654). In the FOLFOXIRI+BEV vs. CAPOXIRI+BEV arms, the 2-year OS rate (95% CI) was 65.5% (49.5%-77.6%) vs. 74.3% (59.8%-84.2%), and the ORR (95% CI) was 76.5% (62.5%-87.2%) vs. 84.6% (71.9%-93.1%). Major (grade ≥3) AEs in the FOLFOXIRI+BEV vs. CAPOXIRI+BEV arms were neutropenia (68.6% vs. 40.4%), febrile neutropenia (9.8% vs. 11.5%), diarrhea (7.8% vs. 17.3%), and appetite loss (7.8% vs. 17.3%)., Conclusion: CAPOXIRI+BEV was well tolerated with reduced hematological toxicity and efficacy comparable to those of FOLFOXIRI+BEV, providing a potentially convenient first-line treatment alternative to FOLFOXIRI+BEV in patients with mCRC., Funding: Chugai Pharmaceutical Co., Ltd., Competing Interests: Declaration of interests H.B. received grants from Ono Pharmaceutical. H.B. also reports honoraria for lectures from Ono Pharmaceutical, Eli Lilly Japan, and Taiho Pharmaceutical. D.K. reports honoraria from Takeda Pharmaceutical, Chugai Pharmaceutical, Novartis, Eli Lilly, Seagen, MSD, Ono Pharmaceutical, Eisai, Taiho Pharmaceutical, Bristol Myers Squibb, Daiichi-Sankyo, Pfizer, Merck Biopharma, and Sysmex and research funding from Ono Pharmaceutical, MSD, Novartis, Servier, Janssen, IQVIA, Syneoshealth, CIMIC, and Cimic Shift Zero. H.S. received grants from Ono Pharmaceutical, Daiichi Sankyo, Taiho Pharmaceutical, and Sanofi and reports honoraria from Bayer, Bristol-Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly Japan, Merck Bio Pharma, MSD, Ono Pharmaceutical, Sanofi, Taiho Pharmaceutical, Takeda Pharmaceutical, and Yakult Honsha. T.H. reports honoraria for lectures from Chugai Pharmaceutical. M.S. is on the speakers’ bureau at Johnson & Johnson, Kaken Pharmaceutical, Eli Lilly Japan, Merck Serono, Ono Pharmaceutical, Taiho Pharmaceutical, Takeda Pharmaceutical, and Yakult Honsha. M.K. reports honoraria for lectures from Chugai Pharmaceutical, Takeda Pharmaceutical, Eli Lilly, Yakult Honsha, and Taiho Pharmaceutical. T. Masuishi reports honoraria from Bayer Yakuhin, Bristol-Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly, Merck Serono, Ono Pharmaceutical, Sanofi, Taiho Pharmaceutical, Takeda Pharmaceutical, and Yakult Honsha and reports research funding from Amgen (Inst), Boehringer Ingelheim (Inst), CMIC (Inst), Daiichi Sankyo (Inst), Eli Lilly Japan (Inst), MSD (Inst), Novartis (Inst), Ono Pharmaceutical (Inst), Pfizer (Inst), and Syneos Health (Inst). H.Y. reports honoraria from Chugai Pharmaceutical and Yakult Honsha. Y. Kagawa reports honoraria from Chugai Pharmaceutical and Yakult Honsha. Y. Komatsu received grants from Ono Pharmaceutical, Chugai Pharmaceutical, Taiho Pharmaceutical, Shionogi, Nippon Zoki Pharmaceutical, Asahi Kasei Pharma Corporation, Nippon Kayaku, Daichi Sankyo, IQVIA Services Japan, MSD, Astellas Pharma, Incyte Corporation, Eisai, National Cancer Center Japan, Syneos Health Clinical, Shift Zero, PARAXEL International, Japan Clinical Cancer Research Organization, EPS Holdings, SYSMEX Corporation, Public Health Research Foundation, Aichi Cancer Center, and the Kyushu Study group of Clinical Cancer and reports honoraria for lectures from Ono Pharmaceutical, Taiho Pharmaceutical, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly and Company, Alfresa Pharma Corporation, Astellas Pharma, EA Pharma, Nippon Kayaku, Pfizer, Nippon Zoki Pharmaceutical, Sanofi, NIPRO, MOROO, Boehringer lngelheim, Hakodate National Hospital, Asahi Kasei Pharma Corporation, MSD, Zeria Pharmaceutical, Bayer Yakuhin, Yakult Honsha, Sumitomo Dainippon Pharma, Incyte Corporation, Merck Biopharma, The Japanese Gastroenterological Association, Sapporo Minami Tokushukai Hospital, and Pancan Japan. E.O. is on the speakers’ bureau at Bristol-Myers Squibb Japan, Chugai Pharmaceutical, Eli Lilly Japan, Ono Pharmaceutical, Taiho Pharmaceutical, and Takeda Pharmaceutical and received research funding from Guardant Health. Y.Y. reports honoraria for lectures from Ono Pharmaceutical, Bristol Myers Squibb, Yakult, Chugai Pharmaceutical, Eli Lily, Bayer, Taiho Pharmaceutical, Servier, Takeda Pharmaceutical, Daiichi Sankyo, Teijin, and Insight. H.K. received grants or contracts from Chugai Pharmaceutical, Taiho Pharmaceutical, and Eisai and received consulting fees from BMS, Eli Lilly Japan, Ono Pharmaceutical, Daiichi Sankyo, and Taiho Pharmaceutical; and has received honoraria from BMS, Bayer Yakuhin, Eli Lilly Japan, MSD, Ono Pharmaceutical, Chugai Pharmaceutical, Daiichi Sankyo, Takeda Pharmaceutical, and Taiho Pharmaceutical. T. Misumi reports honoraria from Chugai Pharmaceutical, AstraZeneca, and Miyarisan. H.T. received lecture fees from Takeda Pharmaceutical, Ono Pharmaceutical, Eli Lilly, Merck Biopharma, and Chugai Pharmaceutical and received research funds from Takeda Pharmaceutical, Daiichi Sankyo, and Ono Pharmaceutical. K.Y. reports honoraria for lectures from Chugai Pharmaceutical, Yakult, Daiichi Sankyo, Merk Serono, Sanofi, MSD, Takeda Pharmaceutical, Taiho Pharmaceutical, Bayer, Eli Lily, Ono Pharmaceutical, and Bristol-Myers Squibb. K.M. reports honoraria from Bristol-Myers Squibb, Daiichi Sankyo, MSD, Eli Lilly, Ono Pharmaceutical, Taiho Pharmaceutical, and Takeda Pharmaceutical; reports a consulting or advisory role at Amgen, Astellas Pharma, AstraZeneca, Chugai Pharmaceutical, and Ono Pharmaceutical; and received research funding from Amgen (Inst), Astellas Pharma (Inst), Chugai Pharmaceutical (Inst), Eisai (Inst), MSD (Inst), Novartis (Inst), Ono Pharmaceutical (Inst), Sanofi (Inst), and Taiho Pharmaceutical (Inst). T.Y. received consulting fees Sumitomo Corporation; received grants from Amgen, Chugai Pharmaceutical, Daiichi Sankyo, Eisai, FALCO biosystems, Genomedia, Molecular Health GmbH, MSD, Nippon Boehringer Ingelheim, Ono Pharmaceutical, Pfizer Japan, Roche Diagnostics, Sanofi, Sysmex, and Taiho Pharmaceutical; and reports honoraria for presentations from Bayer Yakuhin, Chugai Pharmaceutical, Merck Biopharma, MSD, Ono Pharmaceutical, and Takeda Pharmaceutical. T.K. reports honoraria for lectures from Chugai Pharmaceutical, Ono Pharmaceutical, Taiho Pharmaceutical, Takeda Pharmaceutical, and Eli Lilly and Company. A.T. is on the speakers' bureau at Bristol-Myers Squibb, Chugai Pharmaceutical, Eli Lilly Japan, Merck Serono, Sanofi, Taiho Pharmaceutical, and Takeda Pharmaceutical and reports research funding from Ono Pharmaceutical (Inst), Sanofi (Inst), and Taiho Pharmaceutical (Inst)., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

This study evaluated the impacts of management of body condition score (BCS) between pregnancy scanning and lamb marking on the mortality of triplet-bearing ewes and their lambs at 19 research sites across Southern Australia. Triplet-bearing ewes of Maternal (crossbred or composite) or Merino breed were randomly allocated to treatment at pregnancy scanning at an average of 97 days from the start of joining: High or Low BCS. The BCS of individual ewes was assessed at pregnancy scanning, pre-lambing (average of 137 days from the start of joining) and marking (average of 165 days from the end of joining), and ewe and lamb mortality to marking, recorded for each mob. The average BCS at pregnancy scanning was 3.4 for Maternal ewes and 3.3 for Merino ewes. There were no breed by BCS treatment effects on the BCS of ewes at pregnancy scanning or lamb marking or on the change in BCS between pregnancy scanning and pre-lambing or between pre-lambing and marking. The change in BCS differed between the High and Low BCS treatments, between pregnancy scanning and pre-lambing (0.12 vs. −0.33; p < 0.001) and between pre-lambing and marking (−0.39 vs. 0.07; p < 0.001) but did not differ between breeds. The average BCS at marking for ewes managed at the High and Low BCS treatments was 3.1 and 3.0 for Maternals and 3.0 and 2.8 for Merinos. Survival of triplet-bearing Merino ewes (p < 0.01) and their lambs (p < 0.001) was greater when ewes were managed at the High BCS compared to the Low BCS. The BCS treatment did not impact the survival of Maternal ewes or their lambs. The survival of Merino but not Maternal lambs was higher when ewes were in greater BCS pre-lambing (p < 0.01) and when ewes gained BCS between pregnancy scanning and pre-lambing (p < 0.01). Ewe mortality was lower when ewes gained BCS between pregnancy scanning and pre-lambing (p < 0.05). Merino ewes were more likely to die than Maternal ewes for a given change in BCS between pregnancy scanning and pre-lambing (p = 0.065). Overall, our findings demonstrate that producers should manage the nutrition of triplet-bearing Merino ewes so that ewes are in greater BCS at lambing and/or to gain BCS between pregnancy scanning and lambing to improve ewe and lamb survival. Triplet-bearing Maternal ewes should be managed to gain BCS between pregnancy scanning and lambing to improve ewe survival.

Industry consultation in Australia revealed that the potential impact of the mob size of ewes during lambing on the survival of triplet-born lambs was an important research priority. Previous research has demonstrated that smaller mob sizes at lambing improve the survival of single- and especially twin-born lambs, regardless of ewe stocking rate. Therefore, we hypothesised that lambing triplet-bearing ewes in smaller mobs, regardless of stocking rate, will increase the survival of their lambs. Research sites were established on 12 commercial sheep farms across southern Australia between 2019 and 2021. One farm used Merinos whilst the remainder of the farms used non-Merino breeds, consisting of composite ewes joined to composite or terminal sires. Three of the farms were used in two years of the experiment. Adult, triplet-bearing ewes were randomly allocated into one of two treatments, ‘High’ or ‘Low’ mob size, at an average of 135 days from the start of joining. Ewe and lamb survival were assessed between allocation to treatments and lamb marking. Lamb survival was significantly greater for lambs born in the Low (65.6%) compared with the High (56.6%) mob size treatments (p < 0.001). There was no effect of mob size at lambing on the mortality of triplet-bearing ewes. Analysis of the effect of the actual mob sizes showed that reducing the mob size at lambing by 10 triplet-bearing ewes increased the survival of their lambs to marking by 1.5% (p < 0.001). This study has shown that the survival of triplet-born lambs can be improved by lambing triplet-bearing ewes in smaller mobs regardless of stocking rate when ranging from 0.7–13 ewes/ha.

In this paper, we propose a robust sample generation scheme to construct informative triplets. The proposed hard sample generation is a two-stage synthesis framework that produces hard samples through effective positive and negative sample generators in two stages, respectively. The first stage stretches the anchor-positive pairs with piecewise linear manipulation and enhances the quality of generated samples by skillfully designing a conditional generative adversarial network to lower the risk of mode collapse. The second stage utilizes an adaptive reverse metric constraint to generate the final hard samples. Extensive experiments on several benchmark datasets verify that our method achieves superior performance than the existing hard-sample generation algorithms. Besides, we also find that our proposed hard sample generation method combining the existing triplet mining strategies can further boost the deep metric learning performance. [ABSTRACT FROM AUTHOR]

Objectives: The aims of this study were to investigate the perinatal outcome of dichorionic triamniotic (DCTA) and monochorionic triamniotic (MCTA) triplet pregnancies complicated by twin-twin transfusion syndrome (TTTS) treated with fetoscopic laser photocoagulation (FLP) in two academic fetal centers, and to conduct a systematic review of previously published data to investigate perinatal survival in this targeted population.Methods: The first part of the study was a retrospective cohort study of prospectively collected data of consecutive triplet pregnancies with TTTS that underwent FLP at two fetal treatment centers between 2012 and 2020. Demographic, preoperative and operative variables and postoperative outcome were collected. Perinatal outcomes were investigated. The second part of the study was a systematic review and meta-analysis of studies evaluating the outcome of DCTA and/or MCTA triplet pregnancies, including our cohort study. PubMed, Web of Science and Scopus were searched from inception to September 2020. Primary outcomes were fetal survival (survival to birth), neonatal survival (survival to 28 days of age) and gestational age (GA) at birth.Results: A total of 31 sets of triplets with TTTS managed with FLP were included in the cohort study. Of these, 24 were DCTA and seven were MCTA. There were no significant differences in preoperative and operative variables between the two groups. There were also no significant differences between groups in GA at delivery or perinatal survival rate, including fetal and neonatal survival of at least one triplet, at least two triplets and all three triplets. Nine studies, including our cohort study, were included in the systematic review (156 DCTA and 37 MCTA triplet pregnancies treated with FLP). The overall fetal and neonatal survival was 79% (95% CI, 75-83%) and 75% (95% CI, 71-79%), respectively, in DCTA cases and 74% (95% CI, 52-92%) and 71% (95% CI, 49-89%), respectively, in MCTA cases. The rate of preterm birth before 28 weeks and before 32 weeks' gestation was 14% (95% CI, 4-29%) and 61% (95% CI, 50-72%), respectively, in DCTA triplets and 21% (95% CI, 3-45%) and 82% (95% CI, 62-96%), respectively, in MCTA triplets.Conclusions: Triplet pregnancies with TTTS are at high risk of adverse perinatal outcome and preterm birth, regardless of chorionicity. The rate of survival after FLP in MCTA triplets was higher in our study than that reported in previous studies and is currently comparable with survival in DCTA triplets, which could be due to improved surgical skills. © 2022 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Flavins are photoenzymatic cofactors often exploiting the absorption of light to energize photoinduced redox chemistry in a variety of contexts. Both flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) are used for this function. The study of these photoenzymes has been facilitated using flavin analogs. Most of these analogs involve modification of the flavin ring, and there is recent evidence that adenine (Ade)-modified FAD can affect enzyme turnover, but so far this has only been shown for enzymes where the adenine and flavin rings are close to each other in a stacked conformation. FAD is also stacked in aqueous solution, and its photodynamics are quite different from unstacked FAD or FMN. Oxidized photoexcited FAD decays rapidly, presumably through PET with Ade as donor and Fl* as acceptor. Definitive identification of the spectral signatures of Ade∙+ and Fl∙− radicals is elusive. Here we use the FAD analog Flavin 1,N6-Ethenoadenine Dinucleotide (εFAD) to study how different photochemical outcomes depend on the identity of the Ade moiety in stacked FAD and its analog εFAD. We have used UV–Vis transient absorption spectroscopy complemented by TD-DFT calculations to investigate the excited state evolution of the flavins. In FAD*, no radicals were observed, suggesting that FAD* does not undergo PET. εFAD* kinetics showed a broad absorption band that suggests a charge transfer state exists upon photoexcitation with evidence for radical pair formation. Surprisingly, significant triplet flavin was produced from εFAD* We hypothesize that the dipolar (ε)Ade moieties differentially modulate the singlet–triplet energy gap, resulting in different intersystem crossing rates. The additional electron density on the etheno group of εFAD supplies better orbital overlap with the flavin S1 state, accelerating charge transfer in that molecule. [ABSTRACT FROM AUTHOR]