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Abstract Background Whether patients with cT1 − 2N1M0 breast cancer can benefit from postoperative radiotherapy (RT) after receiving neoadjuvant chemotherapy (NAC) has been controversial. Therefore, the purpose of this study was to explore whether postoperative RT can benefit this group of patients in terms of survival. Methods We used Surveillance, Epidemiology, and End Results (SEER) data to conduct a retrospective review of women with cT1 − 2N1M0 breast cancer diagnosed between 20 and 80 years of age who received NAC between 2010 and 2015. Our study compared the impact of postoperative RT on overall survival (OS) and cancer-specific survival (CSS) in breast cancer patients using propensity score matching (PSM) and performed subgroup analysis. Results This study finally included 1092 cT1 − 2N1M0 breast cancer patients. Regardless of the patient’s PSM status, postoperative RT was significantly associated with OS of cT1- 2N1M0 breast cancer patients who received NAC. Specifically, the 10-year OS rate was 78.7% before PSM matching, compared with 71.1% in patients who did not receive postoperative RT, and the difference was more significant after PSM matching, which was 83.1% and 71.1% respectively. However, postoperative RT did not significantly benefit CSS in patients with cT1 − 2N1M0 breast cancer who received NAC. The 10-year CSS rate was 81.4% VS 76.2% (P = 0.085) before PSM matching and 85.8% VS 76.2%(P = 0.076) after matching. Due to the intersection of OS and CSS curves, this restricted mean survival time (RMST) method was chosen as a supplement. After 60 months, the OS difference in RMST between the postoperative RT group and the non-radiotherapy (noRT) group was 7.37 months (95%CI: 0.54–14.21; P = 0.034), and the CSS difference was 5.18 months (95%CI: -1.31-11.68; P = 0.118). Subgroup analysis found that in patients with right-sided breast cancer, postoperative RT improved the patient’s OS (HR = 0.45, 95%CI: 0.21–0.95, P = 0.037) and CSS (HR = 0.42, 95%CI: 0.18–0.98, P = 0.045). Conclusions Our results showed that additional postoperative RT improved the OS of cT1 − 2N1M0 breast cancer patients who received NAC, but failed to improve their CSS. It is worth noting that in the subgroup analysis of patients with right-sided breast cancer, we observed significant improvements in OS and CSS. And further prospective studies are still needed to verify the effect of postoperative RT in different subgroups.

Abstract Background Leukemia is the tenth most common cause of cancer death worldwide and one of the most important causes of disability. To understand the current status and changing trends of the disease burden of leukemia at the global, regional, and national levels, and to provide a scientific basis for the development of leukemia prevention and treatment strategies. Methods Based on open data from the Global Burden of Disease Study 2019 (GBD 2019), R software was used to calculate estimated annual percentage changes to estimate trends in the age‐standardized incidence (ASIR) and the age‐standardized disability‐adjusted life years (DALY) rate due to leukemia and its major subtypes from 1990 to 2019. Results In 2019, globally, the number of incidences and DALYs of leukemia were 643.6 × 103 (587.0 × 103, 699.7 × 103) and 11,657.5 × 103 (10529.1 × 103, 12700.7 × 103), respectively. The ASIR (estimated annual percentage change (EAPC) = −0.37, 95%UI −0.46 to −0.28) and the age‐standardized DALY rate (EAPC = −1.72, 95%UI −1.80 to −1.65) of leukemia showed a decreasing trend from 1990 to 2019. The APC model analysis showed that the age effect of leukemia risk was a “U”‐shaped distribution of relative risk (RR) with increasing age from 1990 to 2019, globally. The time effect was an increase in incidence rate with increasing years but a decrease in DALY rate with increasing years. The cohort effects of both incidence and DALY rates tended to increase and then decrease with the development of the birth cohort. In 1990 and 2019, smoking, high body‐mass index, occupational exposure to benzene, and occupational exposure to formaldehyde were risk factors for DALY in leukemia, especially in areas with high SDI. Conclusions From 1990 to 2019, the disease burden of leukemia showed a decreasing trend, but it is worth noting that its overall severity is still very high. The disease burden of leukemia varies greatly from region to region, and exclusive strategies for the prevention and treatment of leukemia should be developed according to the economic and cultural development of each region.

Abstract Rumors about COVID-19 have been prevalent around the world during the pandemic. Using a veracity judgment task, the present study investigates whether young adults (N = 112) demonstrated measurable differences in processing COVID-19 rumors during the pandemic. They were instructed to read a statement related to COVID-19 and then to evaluate whether it was true or false. We examine the influence of the content characteristics of the statement and the demographic variables on the reading times, the accuracy rates, and the response times of the veracity judgment. We found that the reading times of rumors were only influenced by the length of rumors. Participants spent more time reading a rumor when it was longer. The length of rumors also influenced the accuracy rates of the veracity judgment. Participants were less accurate when the rumor was longer. Furthermore, we found that participants were faster at correctly rejecting false rumors than at accepting true rumors. Importantly, we found a significant effect of family socioeconomic status (SES) on the accuracy rates for which participants from families with higher SES had higher accuracy rates of veracity judgment. Our results demonstrated that both content characteristics (i.e., length) and demographic variables (i.e., family SES) influenced the veracity judgment of COVID-19 rumors.

Abstract Objectives Overactive bladder (OAB) and dyskinesia are frequent complications in patients with Parkinson’s disease (PD). However, the correlation between OAB and dyskinesia has been insufficiently explored. The purpose of this study was to examine the relationship between dyskinesia, OAB, and clinical characteristics among individuals with PD. Methods 1338 PD patients were included in the present study. Demographic features were compared between patients with or without dyskinesia and OAB symptoms. Logistic regression was conducted on dyskinesia to screen clinically relevant factors. Overactive Bladder Symptom Score (OABSS) was further used to stratify the association between the severity of OAB and the occurrence of dyskinesia. Results This study indicates that both dyskinesia and OAB are significantly related to disease severity and cognitive status. PD patients with dyskinesia and OAB having higher UPDRS scores (p 5) (p 5. Discussion This study provides compelling evidence supporting the strong correlation between OAB and dyskinesia in PD patients, emphasizing the presence of shared pathogenic mechanisms between these two conditions. Our findings underscore the importance of considering both OAB and dyskinesia in the clinical management of PD, investigating the intricate connections between OAB and dyskinesia could unveil valuable insights into the complex pathophysiology of PD and potentially identify novel therapeutic targets for more effective PD treatment strategies.

IntroductionAtherosclerosis is the primary pathological basis of ischemic stroke, and dyslipidemia is one of its major etiological factors. Acute ischemic stroke patients exhibit imbalances in lymphocyte subpopulations, yet the correlation between these dynamic changes in lymphocyte subpopulations and lipid metabolism disorders, as well as carotid atherosclerosis in stroke patients remains poorly understood.MethodsWe retrospectively analyzed the demographic data, risk factors of cerebrovascular disease, laboratory examination (lymphocyte subsets, lipid indexes, etc.), clinical features and c;/]-sity from December 2017 to September 2019 and non-stroke patients with dizziness/vertigo during the same period.ResultsThe results showed that peripheral B lymphocyte proportions are elevated in acute ischemic stroke patients compared with those of the control group (13.6 ± 5.3 vs. 11.7 ± 4.4%, p = 0.006). Higher B lymphocyte proportions are associated with concurrent dyslipidemia, increased levels of vascular risk factors including triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and very-low-density lipoprotein cholesterol (VLDL-C), as well as decreased levels of the protective factor high-density lipoprotein cholesterol (HDL-C). Elevated B lymphocyte proportions are independently correlated with carotid atherosclerosis in stroke patients.DiscussionWe found CD19 positive B Lymphocytes increase after ischemic stroke and correlate with Carotid Atherosclerosis. Lymphocyte subpopulations should be highlighted in stroke patients.

Abstract Background Meningoencephalocele is a rare malformation caused by congenital and acquired lesions. The association between recurrent bacterial meningitis and meningoencephaloceles with cerebrospinal fluid (CSF) leak is reported in the literature. We report a rare case of meningoencephalocele secondary to chronic idiopathic intracranial hypertension as a result of hospitalization repeatedly for meningitis due to the lack of CSF leak. Case presentation This study presents a case of a patient with a decade of recurrent meningitis. With clinical symptoms and imaging examination with chronic idiopathic intracranial hypertension, this patient was diagnosed with meningoencephalocele. With the treatment of acetazolamide to decrease CSF product, the patient had no recurrence of meningitis over the 6-months follow-up period. Conclusion In patients with recurrent intracranial infections but no history of immunodeficiency, cranial trauma, or neurosurgery, the possibility of meningitis should be considered appropriately, even in the absence of CSF otorrhea or rhinorrhea.

Aims: To evaluate the clinical, pathological, and genetic features of patients with riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency (RR-MADD). Methods: Thirty-one patients with RR-MADD admitted to our hospital from January 2005 to November 2020 were enrolled, and their clinical data were collected. Pathological characteristics of the muscle tissue and possible pathogenic gene mutations were analyzed. Results: The most common clinical features in all patients were symmetrical proximal muscle weakness. Laboratory examination revealed elevated levels of creatine kinase, homocysteine, and uric acid, acylcarnitines, and organic acid. The muscle biopsy revealed typical pathological changes like lipid deposition. Genetic analysis identified ETFDH mutations in 29 patients, among which one had homozygotes, 19 had compound heterozygotes, 7 had heterozygous mutations, and 2 had heterozygous mutations of both ETFDH and ETFA. Two patients had no pathogenic gene mutations. All patients were treated with riboflavin, and their symptoms improved, which was consistent with the diagnosis of RR-MADD. Conclusion: The clinical manifestations and genetic test results of patients with RR-MADD are heterogeneous. Therefore, a comprehensive analysis of clinical, pathological, and genetic testing is essential for the early diagnosis of RR-MADD.

Abstract Background Hereditary spastic paraplegia 7 (SPG7) is one of the subtypes of autosomal-recessive hereditary spastic paraplegia, which is a clinically heterogeneous neurodegenerative disorder. SPG7 often displays a complicated phenotype, including optic atrophy, ophthalmoparesis, and impaired emotional communication. In the Chinese population, sporadic cases of SPG7 variant-associated spastic ataxia are rarely reported. Case presentation We carefully analysed the clinical features, imaging and genetic tests of two sporadic patients with SPG7, both from the Hebei region of China. One patient presented with progressive bilateral lower limb weakness, spastic-ataxia and no cognitive impairment. Brain MRI revealed mild cerebellar atrophy. Genetic analysis revealed c.1150_1151insCTAC (p.G384Afs*13) frameshift variant and exon1-3 heterozygous deletion. The other patient presented with progressive bilateral lower limb weakness, ataxia, dysarthria and a mild psychosis associated with persecutory delusions, which drew almost no attention, in addition to mild cognitive impairments characterized by a decrease in verbal memory and executive function. Genetic analysis identified two heterozygous variants in the SPG7 gene: c.1150_1151insCTAC (p.G384Afs*13) and c.1496delC (p.Q500Sfs*13). Conclusions The c.1496delC (p.Q500Sfs*13) variant in exon 11 has not been reported before. The c.1150_1151insCTAC variant is speculated to be a hotspot variant in the Chinese population. Patients with SPG7 may have cognitive impairments and psychosis, displaying specific characteristics, which should be of concern.

In order to improve the understanding of the microphysical characteristics of raindrop size distribution (DSD) under different rainfall rates (R) classes, and broaden the knowledge of the impact of radar wavelengths and R classes on the QPE of dual-polarization radars in the Tianshan Mountains, a typical arid area in China, we investigated the microphysical characteristics of DSD across R classes and dual-polarimetric radar QPE relationships across radar wavelengths and R classes, based on the DSD data from a PARSIVEL2 disdrometer at Zhaosu in the Tianshan Mountains during the summers of 2020 and 2021. As the R class increased, the DSD became wider and flatter. The mean value of the mass-weighted mean diameters (Dm) increased, while the mean value of logarithm normalized intercept parameters (log10 Nw) decreased after increasing from C1 to C3, as the R class increased. The largest contributions to R and the radar reflectivity factor from large raindrops (diameter > 3 mm) accounted for approximately 50% and 97%, respectively, while 84% of the total raindrops were small raindrops (diameter < 1 mm). Dual-polarization radars—horizontal polarization reflectivity (Zh), differential reflectivity (Zdr), and specific differential phase (Kdp)—were retrieved based on the DSD data using the T-matrix scattering method. The DSD-based polarimetric radar QPE relations of a single-parameter (R(Zh), R(Kdp)), and double-parameters (R(Zh,Zdr), R(Kdp,Zdr)) on the S-, C-, and X-bands were derived and evaluated. Overall, the performance of the R(Kdp) (R(Kdp,Zdr)) scheme was better than that of R(Zh) (R(Zh,Zdr)) for the QPE in the three bands. Furthermore, we have for the first time confirmed and quantified the performance differences in the QPE relationship of dual-polarization radars under different schemes, radar wavelengths, and R classes in typical arid areas of China. Therefore, selecting an appropriate dual-polarization radar band and QPE scheme for different R classes is necessary to improve the QPE ability compared with an independent scheme under all R classes.

DNAJB6 was identified as the causative gene of limb-girdle muscular dystrophy type 1D. In recent years, the phenotypic and molecular spectrum of DNAJB6-myopathy has been expanded, and several mutations of DNAJB6 have been identified in Europe, North America, and Asia. Interestingly, almost all identified mutations in previous reports were point mutations, and most of them were clustered in exon 5, which encodes the G/F domain of DNAJB6. The so-far unique splice site mutation eliminating the entire G/F domain was reported to cause a severe, early-onset phenotype. Here, we report a juvenile-onset Chinese patient who presented with proximal–distal myopathy as well as esotropia and facial weakness. Muscle pathology showed rimmed vacuolation and myofibrillar disarrangement. A novel splice-site mutation NM_058246:c.236-1_240delGGTGGA of the DNAJB6 gene was identified by targeted exome sequencing, which results in a severe defect of the G/F domain. This rare mutation type expands the molecular spectrum of DNAJB6-myopathy and further underlines the importance of the G/F region.

Abstract The microphysical processes of cloud and precipitation in the Tianshan Mountains still remain unclear due to the complex terrain and the lack of ground‐based observational data. In this study, the characteristics of summer raindrop size distribution (RSD) in the western and central Tianshan Mountains of China were investigated in 2020 and 2021. According to the average raindrop spectra, the RSD characteristics exhibit significant differences that the concentration of medium and large particles is relatively higher at Zhaosu than that at Tianchi. Weak precipitation prevails in the Tianshan Mountains most of the time, yet moderate rainfall and heavy rainfall have a great impact on the accumulated rainfall amount. For each rainfall rate class, raindrops of diameter less than 0.75mm have a lower concentration and raindrops of diameter greater than 3 mm have a higher concentration at Zhaosu as compared to those at Tianchi. Compared with Tianchi, Zhaosu has a larger mass‐weighted mean diameter (Dm) and a lower normalized intercept parameter (log10Nw). Compared with the classical convective spectrum, the RSDs at both Zhaosu and Tianchi are similar to the continental convective cluster. The relationships between the shape and slope (μ–Λ), and radar reflectivity and rainfall rate (Z–R) exhibit a significant difference in the western and central Tianshan Mountains of China.

Mutations in leucine-rich repeat kinase 2 gene (LRRK2) are the most frequent genetic factors contributing to Parkinson's disease (PD). G2385R-LRRK2 increases the risk for PD susceptibility in the Chinese population. However, the pathological role of G2385R-LRRK2 is not clear. In this study, we investigate the roles of G2385R-LRRK2 in neurodegeneration underlying PD pathogenesis using cell biology and pharmacology approaches. We demonstrated that expression of G2385R-LRRK2-induced neurotoxicity in human neuroblastoma SH-SY5Y and mouse primary neurons. G2385R-LRRK2 increased mitochondrial ROS, activates caspase-3/7, and increased PARP cleavage, resulting in neurotoxicity. Treatment with curcumin (an antioxidant) significantly protected against G2385R-LRRK2-induced neurodegeneration by reducing mitochondrial ROS, caspase-3/7 activation, and PARP cleavage. We also found that the cellular environmental stressor, H2O2 significantly promotes both WT-LRRK2- and G2385R-LRRK2-induced neurotoxicity by increasing mitochondrial ROS, caspase-3/7 activation, and PARP cleavage, while curcumin attenuated this combined neurotoxicity. These findings not only provide a novel understanding of G2385R roles in neurodegeneration and environment interaction but also provide a pharmacological approach for intervention for G2385R-LRRK2-linked PD.

Reversible splenial lesion syndrome (RESLES) is a rare clinical imaging syndrome that is characterized by magnetic resonance imaging (MRI) findings of reversible abnormal signals in the splenium of the corpus callosum (SCC). There are a variety of pathogenic causes, including infection, metabolic disturbances, and antiepileptic drug use. Moreover, the disease is clinically rare and easily misdiagnosed. Here, we report a unique case of a 32-year-old man with Fanconi syndrome who had an intensified signal in the SCC and diffuse white matter swelling on MRI. We believe this to be the first adult case of RESLES as a manifestation of Fanconi syndrome, which further expands the disease spectrum leading to RESLES. The imaging features of this case included extensive lesions, symmetrical diffuse restricted signals, and reversibility. The identification of these features improves our understanding of the imaging characteristics of RESLES, thus enabling clinicians to better understand this disease, correctly establish its diagnosis, and improve its prognosis in this kind of patient.

Raindrop size distribution (DSD) is of great significance for understanding the microphysical process of rainfall and the quantitative precipitation estimation (QPE). However, in the past, there was a lack of relevant research on Xinjiang in the arid region of northwest China. In this study, the rainy season data collected by the disdrometer in the Yining area of Xinjiang were used for more than two years, and the characteristics of DSDs for all samples, for two rain types (convective and stratiform), and for six different rain rates were studied. The results showed that nearly 70% of the total samples had a rainfall rate of less than 1 mm·h−1, the convective rain was neither continental nor maritime, and there was a clear boundary between convective rain and stratiform rain in terms of the scattergram of the standardized intercept parameter (log10Nw) versus the mass-weighted average diameter (Dm). When the raindrop diameter was less than 0.7 mm, DSDs of the two rainfalls basically coincided, while when the raindrop diameter was greater than 0.7 mm, DSDs of convective rainfall were located above the stratiform rain. As the rainfall rate increased, Dm increased, while log10Nw first increased and then decreased. In addition, we deduced the Z−R (radar reflectivity-rain rate) relationship and μ−Λ relationship (shape parameter-slope parameter of the gamma DSDs) suitable for the Yining area. These conclusions are conducive to strengthening the understanding of rainfall microphysical processes in arid regions and improving the ability of QPE in arid regions.

We report a family with riboflavin-reactive multiple acyl-CoA dehydrogenase deficiency (RR-MADD) partially caused by a novel mutation in the electron transfer flavoprotein dehydrogenase gene (ETFDH ). The RR-MADD family was identified by physical examination, electromyography, and muscle biopsy of the proband. Laboratory examination and electromyography suggested a muscle disease of the lipid storage myopathies. This was confirmed by a muscle biopsy that revealed lipid deposition in the muscle fibers. The proband’s sister previously had a similar disease, so the family underwent genetic testing. This revealed complex heterozygous ETFDH mutations c.389A > T (p. D130V) and c.1123C > A (p. P375T) in the proband and her sister, of which c.1123C > A (p. P375T) is a novel pathogenic mutation. The proband was treated with riboflavin and changes in physical symptoms and laboratory tests were evaluated before and after treatment. The discovery of a novel locus further expands the ETFDH mutation spectrum and suggests that genotyping is vital for early detection of RR-MADD as it can greatly improve the prognosis.

Mutations in transmembrane protein 230 (TMEM230) gene are suggested to be associated with the autosomal dominant Parkinson’s disease (PD) with typical movement disorders and Lewy body pathology. However, the normal functions and the pathological roles of TMEM230 are not clear. In this study, we used TMEM230 isoform II constructs including wild-type (WT) and four reported PD-linked mutation constructs (Y92C, R141L, 184Wext*5, and 184PGext*5). Ectopic expression of WT and PD-linked mutant TMEM230 variants in cultured cells dramatically induced apoptotic cell death compared with that of vector control cells. Mutant TMEM230 caused cell toxicity at an increased severity than WT TMEM230. Moreover, expression of TMEM230 increased mitochondrial reactive oxygen species (ROS) levels, decreased cellular ATP, activated caspase 3/7, and increased poly(ADP-ribose) polymerase-1 (PARP1) cleavage. Treatment with N-acetylcysteine (NAC; an ROS scavenger) or Z-VAD-FMK (a caspase inhibitor) significantly attenuated TMEM230-induced apoptosis in both cultured cells and primary neurons. Our results indicated that TMEM230 mediated a PARP1-linked apoptotic cell death pathway. These findings not only provide the novel insight into the biological roles of TMEM230 in the PARP1-linked pathway but also provide a TMEM230-induced cell death mechanism underlying PD pathogenesis.

GyrI-like proteins are small-molecule binding proteins that are widely distributed in prokaryotes and eukaryotes, with functions that are poorly characterized. Here, the authors identify GyrI-like proteins as cyclopropanoid cyclopropyl hydrolases that can confer resistance to cytotoxic cyclopropanoid compounds.

Observation data from March to May 2020 of the Ka-band millimeter-wave cloud radar and disdrometer, located in Xinjiang, a typical arid region of China, were used to study the diurnal variation of clouds and precipitation, raindrop size distribution (DSD), and the physical parameters of raindrops. The results showed that there are conspicuous diurnal changes in clouds and precipitation. There is a decreasing trend of the cloud base height (CBH) from 05:00 to 19:00 CST (China Standard Time, UTC +8) and a rising trend of CBHs from 20:00 to 04:00 CST. The cloud top height (CTH) and the cloud thickness show a rising trend from 03:00 to 05:00 CST, 12:00 to 14:00 CST, and 20:00 to 01:00 CST. The diurnal variation of clouds is mainly driven by wind and temperature closely related to the topography of the study area. There are three apparent precipitation periods during the day, namely, 02:00–09:00 CST, 12:00 CST, and 17:00–21:00 CST. The changes in the physical parameters of raindrops are more drastic and evident with a lower CBH, lower CTH, and higher number of cloud layers from 12:00 to 21:00 CST than other times, which are closely related to day-to-day variations of systems moving through, and incoming solar radiation and the mountain–valley wind circulation caused by the trumpet-shaped topography that opens to the west played a secondary role. The DSD is in agreement with a normalized gamma distribution, and the value of the shape factor μ is significantly different from the fixed μ value in the Weather Research and Forecasting (WRF) Model. The rain in arid Xinjiang had a higher concentration of raindrops and a smaller average raindrop diameter than the rain in other humid regions of the Central and Southeast Asian continent. In the Z−R (radar reflectivity–rain rate) relationship, Z=249R1.20 is derived for stratiform rain, and it is significantly different from humid regions. Using Z/Dm (mass–weighted mean diameter) and R, a new empirical relationship Z/Dm=214R1.20 is established, and improvement is obtained in rain retrieval by using the Z/Dm−R relation relative to the conventional Z−R relation. Additionally, the Nt−R, Dm−R, Nw−R, and Nt−Nw relationships with larger differences from humid regions are established by fitting the power-law equations. These results are useful for improving the data parameters of microphysical processes of WRF and the accuracy of quantitative precipitation estimation in arid regions.

The DEAD-box adenosine triphosphatase (ATPase) Prp5p facilitates U2 small nuclear ribonucleoprotein particle (snRNP) binding to the intron branch site region during spliceosome assembly. We present crystal structures of S. cerevisiae Prp5p alone and in complex with ADP at 2.12 Å and 1.95 Å resolution. The three-dimensional packing of Prp5p subdomains differs strikingly from that so far observed in other DEAD-box proteins: two RecA-like subdomains adopt an “open state” conformation stabilized by extensive interactions involving sequences that flank the two subdomains. This conformation is distinct from that required for ATP hydrolysis. Consistent with this, Prp5p mutations that destabilize interdomain interactions exhibited increased ATPase activity in vitro and inhibited splicing of suboptimal branch site substrates in vivo, whereas restoration of interdomain interactions reversed these effects. We conclude that the Prp5p open state conformation is biologically relevant and that disruption of the interdomain interaction facilitates a large-scale conformational change of Prp5p during U2 snRNP-branch site recognition.