Structure-preserved dimension reduction using joint triplets sampling for multi-batch integration of single-cell transcriptomic data.

Dimension reduction (DR) plays an important role in single-cell RNA sequencing (scRNA-seq), such as data interpretation, visualization and other downstream analysis. A desired DR method should be applicable to various application scenarios, including identifying cell types, preserving the inherent structure of data and handling with batch effects. However, most of the existing DR methods fail to accommodate these requirements simultaneously, especially removing batch effects. In this paper, we develop a novel structure-preserved dimension reduction (SPDR) method using intra- and inter-batch triplets sampling. The constructed triplets jointly consider each anchor's mutual nearest neighbors from inter-batch, k-nearest neighbors from intra-batch and randomly selected cells from the whole data, which capture higher order structure information and meanwhile account for batch information of the data. Then we minimize a robust loss function for the chosen triplets to obtain a structure-preserved and batch-corrected low-dimensional representation. Comprehensive evaluations show that SPDR outperforms other competing DR methods, such as INSCT, IVIS, Trimap, Scanorama, scVI and UMAP, in removing batch effects, preserving biological variation, facilitating visualization and improving clustering accuracy. Besides, the two-dimensional (2D) embedding of SPDR presents a clear and authentic expression pattern, and can guide researchers to determine how many cell types should be identified. Furthermore, SPDR is robust to complex data characteristics (such as down-sampling, duplicates and outliers) and varying hyperparameter settings. We believe that SPDR will be a valuable tool for characterizing complex cellular heterogeneity.

Identifying and characterizing drug sensitivity-related lncRNA-TF-gene regulatory triplets.

Recently, many studies have shown that lncRNA can mediate the regulation of TF-gene in drug sensitivity. However, there is still a lack of systematic identification of lncRNA-TF-gene regulatory triplets for drug sensitivity. In this study, we propose a novel analytic approach to systematically identify the lncRNA-TF-gene regulatory triplets related to the drug sensitivity by integrating transcriptome data and drug sensitivity data. Totally, 1570 drug sensitivity-related lncRNA-TF-gene triplets were identified, and 16 307 relationships were formed between drugs and triplets. Then, a comprehensive characterization was performed. Drug sensitivity-related triplets affect a variety of biological functions including drug response-related pathways. Phenotypic similarity analysis showed that the drugs with many shared triplets had high similarity in their two-dimensional structures and indications. In addition, Network analysis revealed the diverse regulation mechanism of lncRNAs in different drugs. Also, survival analysis indicated that lncRNA-TF-gene triplets related to the drug sensitivity could be candidate prognostic biomarkers for clinical applications. Next, using the random walk algorithm, the results of which we screen therapeutic drugs for patients across three cancer types showed high accuracy in the drug-cell line heterogeneity network based on the identified triplets. Besides, we developed a user-friendly web interface-DrugSETs (http://bio-bigdata.hrbmu.edu.cn/DrugSETs/) available to explore 1570 lncRNA-TF-gene triplets relevant with 282 drugs. It can also submit a patient's expression profile to predict therapeutic drugs conveniently. In summary, our research may promote the study of lncRNAs in the drug resistance mechanism and improve the effectiveness of treatment.

Perinatal outcomes and growth discordance of triplet pregnancies based on chorionicity: a retrospective cohort study.

BACKGROUND: The worldwide occurrence of triplet pregnancy is estimated to be 0.093%, with a natural incidence of approximately 1 in 8000. This study aims to analyze the neonatal health status and birth weight discordance (BWD) of triplets based on chorionicity from birth until discharge. METHODS: This was a retrospective study. We reviewed a total of 136 triplet pregnancies at our tertiary hospital between January 1, 2001, and December 31, 2021. Maternal and neonatal outcomes, inter-triplet BWD, neonatal morbidity, and mortality were analyzed. RESULTS: Among all cases, the rates of intrauterine death, neonatal death, and perinatal death were 10.29, 13.07, and 24.26%, respectively. Thirty-seven of the cases resulted in fetal loss, including 13 with fetal anomalies. The maternal complications and neonatal outcomes of the 99 triplet pregnancies without fetal loss were compared across different chorionicities, including a dichorionic (DC) group (41 cases), trichorionic (TC) group (37 cases), and monochorionic (MC) group (21 cases). Neonatal hypoproteinemia (P < 0.001), hyperbilirubinemia (P < 0.019), and anemia (P < 0.003) exhibited significant differences according to chorionicity, as did the distribution of BWD (P < 0.001). More than half of the cases in the DC and TC groups had a BWD < 15%, while those in the MC group had a BWD < 50% (47.6%). TC pregnancy decreased the risk of neonatal anemia (adjusted odds ratio [AOR] = 0.084) and need for blood transfusion therapy after birth (AOR = 0.119). In contrast, a BWD > 25% increased the risk of neonatal anemia (AOR = 10.135) and need for blood transfusion after birth (AOR = 7.127). TC pregnancy, MCDA or MCTA, and BWD > 25% increased neonatal hypoproteinemia, with AORs of 4.629, 5.123, and 5.343, respectively. CONCLUSIONS: The BWD differed significantly according to chorionicity. Additionally, TC pregnancies reduced the risk of neonatal anemia and need for blood transfusion, but increased the risk of neonatal hypoproteinemia. In contrast, the BWD between the largest and smallest triplets increased the risk of neonatal anemia and the need for blood transfusion. TC pregnancy, MCDA or MCTA, and BWD > 25% increased the risks of neonatal hypoproteinemia. However, due to the limited number of triplet pregnancies, further exploration of the underlying mechanism is warranted.

Pregnancy outcomes of monochorionic diamniotic and dichorionic diamniotic twin pregnancies conceived by assisted reproductive technology and conceived naturally: a study based on chorionic comparison.

OBJECTIVE: To evaluate monochorionic diamniotic (MCDA) and dichorionic diamniotic (DCDA) twin pregnancies conceived by assisted reproductive technology (ART) and conceived naturally. METHODS: We retrospectively analyzed the data on twin pregnancies conceived by ART from January 2015 to January 2022,and compared pregnancy outcomes of MCDA and DCDA twins conceived by ART with those of MCDA and DCDA twins conceived naturally, pregnancy outcomes between MCDA and DCDA twins conceived by ART, and pregnancy outcomes of DCT and TCT pregnancies reduced to DCDA pregnancies with those of DCDA pregnancies conceived naturally. RESULT: MCDA pregnancies conceived by ART accounted for 4.21% of the total pregnancies conceived by ART and 43.81% of the total MCDA pregnancies. DCDA pregnancies conceived by ART accounted for 95.79% of the total pregnancies conceived by ART and 93.26% of the total DCDA pregnancies. Women with MCDA pregnancies conceived by ART had a higher premature delivery rate, lower neonatal weights, a higher placenta previa rate, and a lower twin survival rate than those with MCDA pregnancies conceived naturally (all p < 0.05). Women with DCDA pregnancies conceived naturally had lower rates of preterm birth, higher neonatal weights, and higher twin survival rates than women with DCDA pregnancies conceived by ART and those with DCT and TCT pregnancies reduced to DCDA pregnancies (all p < 0.05). CONCLUSION: Our study confirms that the pregnancy outcomes of MCDA pregnancies conceived by ART are worse than those of MCDA pregnancies conceived naturally. Similarly, the pregnancy outcomes of naturally-conceived DCDA pregnancies are better than those of DCDA pregnancies conceived by ART and DCT and TCT pregnancies reduced to DCDA pregnancies.

The outcome of reduced and non-reduced triplet pregnancies managed in a tertiary hospital during a 15-year-period - a retrospective cohort study.

OBJECTIVES: Triplet pregnancies involve several complications, the most important being prematurity as virtually all triplets are born preterm. We conducted this study to compare the outcomes of reduced vs. non-reduced triplet pregnancies managed in the largest tertiary hospital in Finland. METHODS: This was a retrospective cohort study in the Helsinki University Hospital during 2006-2020. Data on the pregnancies, parturients and newborns were collected from patient records. The fetal number, chorionicity and amnionicity were defined in first-trimester ultrasound screening. The main outcome measures were perinatal and neonatal mortality of non-reduced triplets, compared to twins and singletons selectively reduced of triplet pregnancies. RESULTS: There were 57 initially triplet pregnancies and 35 of these continued as non-reduced triplets and resulted in the delivery of 104 liveborn children. The remaining 22 cases were spontaneously or medically reduced to twins (9) or singletons (13). Most (54.4 %) triplet pregnancies were spontaneous. There were no significant differences in gestational age at delivery between triplets (mean 33+0, median 34+0) and those reduced to twins (mean 32+5, median 36+0). The survival at one week of age was higher for triplets compared to twins (p<0.00001). CONCLUSIONS: Most pregnancies continued as non-reduced triplets, which were born at a similar gestational age but with a significantly higher liveborn rate compared to those reduced to twins. There were no early neonatal deaths among cases reduced to singletons. Prematurity was the greatest concern for multiples in this cohort, whereas the small numbers may explain the lack of difference in gestational age between these groups.

Multifetal pregnancy reductions and selective fetocide in a tertiary referral center - a retrospective cohort study.

OBJECTIVES: Multiple pregnancies involve several complications, most often prematurity, but also higher anomaly rates. Reducing fetuses generally improves pregnancy outcomes. We conducted this study to evaluate the obstetrical and neonatal results after multifetal pregnancy reduction (MFPR) in the largest tertiary hospital in Finland. METHODS: This retrospective cohort study included all MFPR managed in Helsinki University Hospital during a 13 year period (2007-2019). Data on pregnancies, parturients and newborns were collected from patient files. The number of fetuses, chorionicities and amnionicities were defined in first-trimester ultrasound screening. RESULTS: There were 54 MFPR cases included in the final analyses. Most often the reduction was from twins to singletons (n=34, 63 %). Majority of these (25/34, 73.5 %) were due to co-twin anomaly. Triplets (n=16, 29.6 %) were reduced to twins (n=7, 13 %) or singletons (n=9, 16.7 %), quadruplets (n=2, 3.7 %) and quintuplets (n=2, 3.7 %) to twins. Most (33/54, 61.1 %) MFPR procedures were done by 15+0 weeks of gestation. There were six miscarriages after MFPR and one early co-twin miscarriage. In the remaining 47 pregnancies that continued as twins (n=7, 14.9 %) or singletons (n=40, 85.1 %) the liveborn rate was 90 % for one fetus and 71.4 % for two fetuses. CONCLUSIONS: Most MFPR cases were pregnancies with an anomalous co-twin. The whole pregnancy loss risk was 11.1 % after MFPR. The majority (70.6 %) of twins were spontaneous, whereas all quadruplets, quintuplets, and 56.3 % of triplets were assisted reproductive technologies (ART) pregnancies. Careful counselling should be an essential part of obstetrical care in multiple pregnancies, which should be referred to fetomaternal units for MFPR option.

First case of dichorionic diamniotic triplet pregnancy after single blastocyst transfer.

Multiple pregnancies are associated with significant maternal, fetal, and neonatal risks, including prematurity, low birth weight, pre-eclampsia, anemia, postpartum hemorrhage, intrauterine growth restriction, neonatal morbidity, and increased neonatal and infant mortality rates. Assisted reproductive technology (ART) treatments should prioritize efforts to reduce such events, resisting patient demand for the transfer of multiple embryos at each transfer to increase success rates. Extended culture, embryo selection, and single blastocyst transfer can mitigate the risk of high-order multiple pregnancies. Intriguingly, elective single-embryo transfer (eSET) greatly reduces, but does not completely eliminate, the likelihood of multiple gestations. The occurrence of monozygotic twinning (MZT) gives rise to identical twins. It is more prevalent in women undergoing in vitro fertilization (IVF) compared with natural conception. In fact, the reported risks of monozygotic twinning in IVF and natural conception are 1.7 and 0.4%, respectively. The factors suspected to increase the risk of MZT in IVF are multiple embryo transfer, micromanipulation, and extended in vitro culture. Determining chorionicity and amnionicity is crucial in the assessment of multiple pregnancies during the first-trimester ultrasound examination. Dichorionic twins result from embryo splitting within 3 days after fertilization, while monochorionic twins occur when the splitting takes place between 4 and 8 days after fertilization. These timings are suggested by observations carried out in natural pregnancies. In ART, there is evidence of dichorionic twins derived from single embryo transfer (SET). Here, we report a case of dichorionic diamniotic triplets after a single blastocyst transfer occurred in our center. To our knowledge, this is the first case documented so far.

Intertwin nuchal translucency difference predicts the chance of co-twin death after fetal reduction in dichorionic triplet pregnancies: a retrospective analysis study.

OBJECTIVES: To compare the clinical outcomes of different multifetal pregnancy reduction (MFPR) programs in dichorionic (DC) triplets, and explore the association between early ultrasound characteristics and co-twin death after potassium chloride (KCl) injection into one monochorionic (MC) twin. METHODS: We retrospectively reviewed the data of DC triplets who underwent MFPR at our center during 2012-2021. Patients were grouped as follows: intracardiac KCl injection into one MC twin (group A), intracardiac KCl injection into both MC twins simultaneously (group B), and reduction of the singleton fetus (group C) and pregnancy outcomes were compared. Logistic regression was used to determine whether ultrasound measurements at 11-13+6 weeks predicted co-twin death and the receiver operator characteristic (ROC) analysis was conducted to assess the predictive performance. RESULTS: Finally, we enrolled 184 patients. 153 cases were in group A, and 18, 13 cases were in group B and C respectively. Gestational age at the time of MFPR did not differ among the 3 groups (median: [Formula: see text] weeks). The survival rate was 89.6%, 88.9%, and 92.3% in group A, B, and C respectively, which was comparable among groups. Preterm birth was more common in group C (10/12, 83.3%). After KCl injection into one MC twin, co-twin death occurred in 86.3% cases (132/153) within 1 day; however, 3 patients had 2 live births each, with normal postnatal development. Intertwin nuchal translucency (NT) difference/discordance significantly predicted co-twin death within 1 day after MFPR, and the areas under the ROC curve were 0.694 and 0.689, respectively. CONCLUSIONS: For MFPR in DC triplet pregnancies, reduction of the MC twins results in less preterm birth, and women with KCl injection into either one or both MC twins had similar outcomes. Large intertwin NT difference/discordance was associated with co-twin death within 1 day after KCl injection into one of the MC twins.

Perinatal outcome and long-term hospitalization of triplets according to birth order.

PURPOSE: The association between birth order and adverse perinatal outcomes has been well studied in twin pregnancies. However, little is known about the differences in immediate perinatal outcomes as well as long-term hospitalization of the offspring in triplet pregnancies according to their birth order. As such, we aimed to assess the differences in immediate perinatal outcomes and long-term hospitalizations among triplets by their birth order. METHODS: In a retrospective hospital-based cohort study, immediate perinatal outcomes and long-term hospitalizations were compared among triplet siblings according to their birth order. Deliveries occurred between the years 1991 and 2021 in a tertiary medical center. The study groups were followed until 18 years of age for cardiovascular, respiratory, neurological, and infection-related hospitalizations. Generalized estimation equation (GEE) models were used to control for confounders. Kaplan-Meier survival curves were used to compare cumulative long-term hospitalization incidences and Cox proportional hazards models were performed to control for confounders. RESULTS: The study included 117 triplet deliveries. Rates of small for gestational age (SGA) infants increased linearly by birth order (6.0%, 7.7%, and 15.4% for the first, second, and third siblings, respectively; p-value for trends = 0.035). Using a GEE model controlling for maternal age, being born third in a triplet pregnancy was independently associated with SGA (third vs. first sibling, adjusted OR 3.0, 95% CI 1.38-6.59, p = 0.005). No significant differences in cardiovascular, respiratory, neurological, and infection-related hospitalizations were noted among the first, second, and third siblings. Likewise, using Kaplan-Meier survival analyses, no significant differences in the cumulative incidence of long-term pediatric hospitalizations were noted between the siblings. In Cox proportional hazards models, controlling for weight and gender, birth order in a triplet pregnancy did not exhibit an association with long-term hospitalizations of the offspring. CONCLUSION: Despite the association between birth order and SGA, birth order in triplets does not seem to have an impact on the risk for long-term offspring hospitalization.

Triplet Generation Through Singlet Fission in Metal-Organic Framework: An Alternative Route to Inefficient Singlet-Triplet Intersystem Crossing.

High quantum yield triplets, populated by initially prepared excited singlets, are desired for various energy conversion schemes in solid working compositions like porous MOFs. However, a large disparity in the distribution of the excitonic center of mass, singlet-triplet intersystem crossing (ISC) in such assemblies is inhibited, so much so that a carboxy-coordinated zirconium heavy metal ion cannot effectively facilitate the ISC through spin-orbit coupling. Circumventing this sluggish ISC, singlet fission (SF) is explored as a viable route to generating triplets in solution-stable MOFs. Efficient SF is achieved through a high degree of interchromophoric coupling that facilitates electron super-exchange to generate triplet pairs. Here we show that a predesigned chromophoric linker with extremely poor ISC efficiency (kISC ) but E S 1 ≥ 2 E T 1 ${{E}_{{S}_{1}}\ge {2E}_{{T}_{1}}}$ form triplets in MOF in contrast to the frameworks that are built from linkers with sizable kISC but E S 1 ≤ 2 E T 1 ${{E}_{{S}_{1}}\le {2E}_{{T}_{1}}}$ . This work opens a new photophysical and photochemical avenue in MOF chemistry and utility in energy conversion schemes.

The role of the University of Padua medical school in the study of conjoined twins between 18th and early 19th century.

The Medical School of Padua (Italy) contributed profoundly to the study of teratology. Many famous physicians and professors of medicine, such as Liceti, Vallisneri, Morgagni, and Malacarne, have studied and investigated these anomalies to better understand the causes and to find a potential explanation, often preserving the specimens for future studies. The present study highlights some historical cases of conjoined twins and a conjoined triplet preserved at the Morgagni Museum of Human Anatomy to show the development of medical theories in the teratological field between the 18th and early 19th century. This approach will provide insights into different study methods and ideas of some of the most famous scholars working in Padua at that time. The current article focuses on rare cases, both human and animal, that were encountered by physicians who worked in the Veneto area in the late 18th and early 19th century. Their detailed descriptions are not only of historical but also of contemporary dysmorphological value.

Clinical and genetic characteristics of late-onset Huntington's disease in a large European cohort.

BACKGROUND AND PURPOSE: Huntington's disease (HD) is an autosomal dominant condition caused by CAG-triplet repeat expansions. CAG-triplet repeat expansion is inversely correlated with age of onset in HD and largely determines the clinical features. The aim of this study was to examine the phenotypic and genotypic correlates of late-onset HD (LoHD) and to determine whether LoHD is a more benign expression of HD. METHODS: This was a retrospective observational study of 5053 White European HD patients from the ENROLL-HD database. Sociodemographic, genetic and phenotypic variables at baseline evaluation of subjects with LoHD, common-onset HD (CoHD) and young-onset HD (YoHD) were compared. LoHD subjects were compared with healthy subjects (HS) aged ≥60 years. Differences between the CoHD and LoHD groups were also explored in subjects with 41 CAG triplets, a repeat number in the lower pathological expansion range associated with wide variability in age at onset. RESULTS: Late-onset HD presented predominantly as motor-onset disease, with a lower prevalence of both psychiatric history and current symptomatology. Absent/unknown HD family history was significantly more common in the LoHD group (31.2%) than in the other groups. The LoHD group had more severe motor and cognitive deficits than the HS group. Subjects with LoHD and CoHD with 41 triplets in the larger allele were comparable with regard to cognitive impairment, but those with LoHD had more severe motor disorders, less problematic behaviors and more often an unknown HD family history. CONCLUSIONS: It is likely that cognitive disorders and motor symptoms of LoHD are at least partly age-related and not a direct expression of the disease. In addition to CAG-triplet repeat expansion, future studies should investigate the role of other genetic and environmental factors in determining age of onset.

Concordance for Gender Dysphoria in Genetic Female Monozygotic (Identical) Triplets.

The biopsychosocial etiology of gender dysphoria is poorly understood, but current thought suggests a complex interaction of genetic, hormonal, environmental, and differences in brain development and physiology. Twin studies have implicated a genetic role in the formation of gender identity. Congruence for gender dysphoria is more common among monozygotic twins compared to dizygotic twins. We present a case of monozygotic (identical) triplets who have each transitioned from female to male under the care of a university transgender health service. Each triplet experienced gender dysphoria from childhood and has undergone transitional endocrine care and various aspects of gender-affirming surgery. Although a pure genetic or biological component cannot be attributed as a cause of their gender dysphoria with absolute certainty since the triplets were raised together, this unusual case of gender dysphoria among a set of monozygotic triplets adds support for a heritable role in gender identity formation.

Supporting multiple birth families: Perceptions and experiences of health visitors.

OBJECTIVE: To explore the current practice and perceptions of health visitors in supporting multiple birth families. DESIGN AND SAMPLE: Practicing health visitors across the United Kingdom were invited to complete a cross-sectional, descriptive, online survey. The questionnaire covered multiple birth caseload, education received about multiples and the experience of working with families. Two-hundred and ninety health visitors completed the questionnaire. Descriptive and inferential statistics were used for analysis of the quantitative components and thematic analysis for the qualitative data. RESULTS: Most health visitors had twins on their current workload. Most health visitors had not received any specific training or continuing professional development regarding the needs of multiple birth families. Supporting the families within the confines of reduced time and increased workload was challenging. Daily tasks of caring for multiples were the main areas that health visitors and parents wanted more information about. CONCLUSIONS: In the United Kingdom, health visitors are uniquely positioned to support multiple birth families, in particular during the more challenging early years. However, the findings of this study suggest that many health visitors are aware that the care and support that they are able to provide multiple birth families falls short of meeting their needs.

Spike Timing-Dependent Plasticity with Enhanced Long-Term Depression Leads to an Increase of Statistical Complexity.

Synaptic plasticity is characterized by remodeling of existing synapses caused by strengthening and/or weakening of connections. This is represented by long-term potentiation (LTP) and long-term depression (LTD). The occurrence of a presynaptic spike (or action potential) followed by a temporally nearby postsynaptic spike induces LTP; conversely, if the postsynaptic spike precedes the presynaptic spike, it induces LTD. This form of synaptic plasticity induction depends on the order and timing of the pre- and postsynaptic action potential, and has been termed spike time-dependent plasticity (STDP). After an epileptic seizure, LTD plays an important role as a depressor of synapses, which may lead to their complete disappearance together with that of their neighboring connections until days after the event. Added to the fact that after an epileptic seizure the network seeks to regulate the excess activity through two key mechanisms: depressed connections and neuronal death (eliminating excitatory neurons from the network), LTD becomes of great interest in our study. To investigate this phenomenon, we develop a biologically plausible model that privileges LTD at the triplet level while maintaining the pairwise structure in the STPD and study how network dynamics are affected as neuronal damage increases. We find that the statistical complexity is significantly higher for the network where LTD presented both types of interactions. While in the case where the STPD is defined with purely pairwise interactions an increase is observed as damage becomes higher for both Shannon Entropy and Fisher information.

Identification of hub lncRNA ceRNAs in multiple sclerosis based on ceRNA mechanisms.

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system, and the pathogenesis is influenced by genetic susceptibility. Accumulating evidence has demonstrated that long non-coding RNAs (lncRNAs) play essential roles in complex diseases, including acting as competing endogenous RNAs (ceRNAs). However, the functional roles and regulatory mechanisms of lncRNAs acting as ceRNAs in MS are still unclear. In this study, we identified hub lncRNA ceRNAs in MS based on ceRNA mechanisms and annotated their functions. The lncRNA-associated ceRNA network (LACN) was constructed by integrating the expression profiles of lncRNA/mRNA and miRNA in MS and normal samples, and the experimentally validated interactions of lncRNA-miRNA and mRNA-miRNA. We found three hub lncRNA ceRNAs (XIST, OIP5-AS1, and CTB-89H12.4) using the network analysis and obtained 96 lncRNA-mediated competing triplets (LCTs, lncRNA-miRNA-mRNA) with the hub lncRNA ceRNAs, which constituted 3 hub ceRNA modules. The functional analysis identified 12 pathways enriched by the 3 hub lncRNA ceRNAs, of which 6 were confirmed to be related to MS. For example, XIST was enriched in the 'spliceosome' and 'RNA transport' related to the typing of MS, and CTB-89H12.4 was enriched in the 'mTOR signaling pathway,' a potential therapeutic target for MS. We dissected the expression patterns of the 96 LCTs in MS individually. LCT XIST-miR-326-HNRNPA1, for which the expression pattern in MS revealed that XIST and HNRNPA1 were up-regulated and miR-326 was down-regulated, consisted of risk RNAs for MS that were validated by other research. Therefore, XIST-miR-326-HNRNPA1 might play a central role in the pathogenesis of MS. These results will contribute to the discovery of novel biomarkers and the development of new therapeutic methods for MS.

Changes in treatment landscape of relapsed or refractory multiple myeloma and their association with mortality: Insights from German claims database.

OBJECTIVES: Emerging treatments for relapsed or refractory multiple myeloma (rrMM) have led to increasing options for many patients. This study aimed to assess changes in utilization of these options in Germany with a focus on modern triplet regimens including new agents, such as carfilzomib, ixazomib, elotuzumab and daratumumab, and to evaluate whether this had an impact on rrMM-related outcomes over time. METHODS: The study population consisted of 1255 rrMM patients who were assigned to one of the following 6 treatment groups: immunomodulatory drug (IMiD)-based doublets, proteasome inhibitor (PI)-based doublets, daratumumab monotherapy, PI-IMiD-based triplets, monoclonal antibodies (mAbs)-based triplets, or other treatment. RESULTS: Use of triplet-based therapy regimens increased from 5.9% in 2014 to 31.4% in 2017. In parallel, use of IMiD-based doublets decreased from 74.3% in 2014 to 37.6% in 2017. Over the same time period, the risk of death decreased by 32% and the risk of hospitalization which was reduced by 30%. The risk for serious adverse events remained unchanged. CONCLUSIONS: Between 2014 and 2017, the use of triplet-based therapy regimens for rrMM in Germany has significantly increased and this was associated with a significant decline in deaths and hospitalizations without an increased incidence of serious adverse events.

Effect of monochorionicity on perinatal outcome and growth discordance in triplet pregnancy: collaborative multicenter study in England, 2000-2013.

OBJECTIVES: To compare perinatal outcome and growth discordance between trichorionic triamniotic (TCTA) and dichorionic triamniotic (DCTA) or monochorionic triamniotic (MCTA) triplet pregnancies. METHODS: This was a multicenter cohort study using population-based data on triplet pregnancies from 11 Northern Survey of Twin and Multiple Pregnancy (NorSTAMP) maternity units and the Southwest Thames Region of London Obstetric Research Collaborative (STORK) multiple pregnancy cohort, for 2000-2013. Perinatal outcomes (from ≥ 24 weeks' gestation to 28 days of age), intertriplet fetal growth and birth-weight (BW) discordance and neonatal morbidity were analyzed in TCTA compared with DCTA/MCTA pregnancies. RESULTS: Monochorionic placentation of a pair or trio in triplet pregnancy (n = 72) was associated with a significantly increased risk of perinatal mortality (risk ratio, 2.7 (95% CI, 1.3-5.5)) compared with that in TCTA pregnancies (n = 68), due mainly to a much higher risk of stillbirth (risk ratio, 5.4 (95% CI, 1.6-18.2)), with 57% of all stillbirth cases resulting from fetofetal transfusion syndrome, while there was no significant difference in neonatal mortality (P = 0.60). The associations with perinatal mortality and stillbirth persisted when considering only pregnancies not affected by a major congenital anomaly. DCTA/MCTA triplets had lower BW and demonstrated greater BW discordance than did TCTA triplets (P = 0.049). Severe BW discordance of > 35% was 2.5-fold higher in DCTA/MCTA compared with TCTA pregnancies (26.1% vs 10.4%), but this difference did not reach statistical significance (P = 0.06), presumably due to low numbers. Triplets in both groups were delivered by Cesarean section in over 95% of cases, at a similar gestational age (median, 33 weeks' gestation). The rate of respiratory (P = 0.28) or infectious (P = 0.08) neonatal morbidity was similar between the groups. CONCLUSIONS: Despite close antenatal surveillance, monochorionic placentation of a pair or trio in triamniotic triplet pregnancy was associated with a significantly increased stillbirth risk, mainly due to fetofetal transfusion syndrome, and with greater size discordance. In liveborn triplets, there was no adverse effect of monochorionicity on neonatal outcome. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Enhancing Biomedical Relation Extraction with Transformer Models using Shortest Dependency Path Features and Triplet Information.

Entity relation extraction plays an important role in the biomedical, healthcare, and clinical research areas. Recently, pre-trained models based on transformer architectures and their variants have shown remarkable performances in various natural language processing tasks. Most of these variants were based on slight modifications in the architectural components, representation schemes and augmenting data using distant supervision methods. In distantly supervised methods, one of the main challenges is pruning out noisy samples. A similar situation can arise when the training samples are not directly available but need to be constructed from the given dataset. The BioCreative V Chemical Disease Relation (CDR) task provides a dataset that does not explicitly offer mention-level gold annotations and hence replicates the above scenario. Selecting the representative sentences from the given abstract or document text that could convey a potential entity relationship becomes essential. Most of the existing methods in literature propose to either consider the entire text or all the sentences which contain the entity mentions. This could be a computationally expensive and time consuming approach. This paper presents a novel approach to handle such scenarios, specifically in biomedical relation extraction. We propose utilizing the Shortest Dependency Path (SDP) features for constructing data samples by pruning out noisy information and selecting the most representative samples for model learning. We also utilize triplet information in model learning using the biomedical variant of BERT, viz., BioBERT. The problem is represented as a sentence pair classification task using the sentence and the entity-relation pair as input. We analyze the approach on both intra-sentential and inter-sentential relations in the CDR dataset. The proposed approach that utilizes the SDP and triplet features presents promising results, specifically on the inter-sentential relation extraction task. We make the code used for this work publicly available on Github.1.

Intrafetal laser therapy in a monochorionic diamniotic triplet pregnancy with two acardiac fetuses: a case report and literature review.

BACKGROUND: Monochorionic diamniotic triplet pregnancies are rare. Twin reversed arterial perfusion sequence in monochorionic triplet pregnancies is extremely rare, and it is associated with high perinatal morbidity and mortality rates in the "pump fetus." CASE PRESENTATION: We reported a case of monochorionic diamniotic triplet pregnancy with twin reversed arterial perfusion sequence, including two acardiac fetuses sharing a single amniotic sac and a normal fetus in another amniotic sac. Due to rapid growth of the acardiac fetuses, intrafetal laser therapy was performed in both of them under ultrasound guidance at 15 weeks +5 days. Subsequently, regular and careful antenatal care including fetal ultrasonography and doppler and fetal echocardiography was conducted. At 37 weeks +4 days, a healthy female baby weighing 2510 g was delivered. The baby was followed up and now at 11 months old is in good health. CONCLUSIONS: Twin reversed arterial perfusion sequence in monochorionic triplet pregnancy should be diagnosed early by ultrasound imaging during pregnancy. Individualized management should be based on clinical conditions to improve the perinatal outcome of the pump twin. Intrafetal laser therapy could be an alternative procedure when intrauterine intervention is required.