A survey of algorithms for the detection of genomic structural variants from long-read sequencing data.

As long-read sequencing technologies are becoming increasingly popular, a number of methods have been developed for the discovery and analysis of structural variants (SVs) from long reads. Long reads enable detection of SVs that could not be previously detected from short-read sequencing, but computational methods must adapt to the unique challenges and opportunities presented by long-read sequencing. Here, we summarize over 50 long-read-based methods for SV detection, genotyping and visualization, and discuss how new telomere-to-telomere genome assemblies and pangenome efforts can improve the accuracy and drive the development of SV callers in the future.

Deep learning-driven adaptive optics for single-molecule localization microscopy.

The inhomogeneous refractive indices of biological tissues blur and distort single-molecule emission patterns generating image artifacts and decreasing the achievable resolution of single-molecule localization microscopy (SMLM). Conventional sensorless adaptive optics methods rely on iterative mirror changes and image-quality metrics. However, these metrics result in inconsistent metric responses and thus fundamentally limit their efficacy for aberration correction in tissues. To bypass iterative trial-then-evaluate processes, we developed deep learning-driven adaptive optics for SMLM to allow direct inference of wavefront distortion and near real-time compensation. Our trained deep neural network monitors the individual emission patterns from single-molecule experiments, infers their shared wavefront distortion, feeds the estimates through a dynamic filter and drives a deformable mirror to compensate sample-induced aberrations. We demonstrated that our method simultaneously estimates and compensates 28 wavefront deformation shapes and improves the resolution and fidelity of three-dimensional SMLM through >130-µm-thick brain tissue specimens.

A map of cis-regulatory elements and 3D genome structures in zebrafish.

The zebrafish (Danio rerio) has been widely used in the study of human disease and development, and about 70% of the protein-coding genes are conserved between the two species1. However, studies in zebrafish remain constrained by the sparse annotation of functional control elements in the zebrafish genome. Here we performed RNA sequencing, assay for transposase-accessible chromatin using sequencing (ATAC-seq), chromatin immunoprecipitation with sequencing, whole-genome bisulfite sequencing, and chromosome conformation capture (Hi-C) experiments in up to eleven adult and two embryonic tissues to generate a comprehensive map of transcriptomes, cis-regulatory elements, heterochromatin, methylomes and 3D genome organization in the zebrafish Tübingen reference strain. A comparison of zebrafish, human and mouse regulatory elements enabled the identification of both evolutionarily conserved and species-specific regulatory sequences and networks. We observed enrichment of evolutionary breakpoints at topologically associating domain boundaries, which were correlated with strong histone H3 lysine 4 trimethylation (H3K4me3) and CCCTC-binding factor (CTCF) signals. We performed single-cell ATAC-seq in zebrafish brain, which delineated 25 different clusters of cell types. By combining long-read DNA sequencing and Hi-C, we assembled the sex-determining chromosome 4 de novo. Overall, our work provides an additional epigenomic anchor for the functional annotation of vertebrate genomes and the study of evolutionarily conserved elements of 3D genome organization.

Mycobacterium vaccae alleviates allergic airway inflammation and airway hyper-responsiveness in asthmatic mice by altering intestinal microbiota.

Host immunity can influence the composition of the gut microbiota and consequently affect disease progression. Previously, we reported that a Mycobacterium vaccae vaccine could ameliorate allergic inflammation in asthmatic mice by regulating inflammatory immune processes. Here, we investigated the anti-inflammatory effects of M. vaccae on allergic asthma via gut microbiota modulation. An ovalbumin (OVA)-induced asthmatic murine model was established and treated with M. vaccae. Gut microbiota profiles were determined in 18 BALB/c mice using 16S rDNA gene sequencing and metabolomic profiling was performed using liquid chromatography quadrupole time-of-flight mass spectrometry. Mycobacterium vaccae alleviated airway hyper-reactivity and inflammatory infiltration in mice with OVA-induced allergic asthma. The microbiota of asthmatic mice is disrupted and that this can be reversed with M. vaccae. Additionally, a total of 24 differential metabolites were screened, and the abundance of PI(14:1(9Z)/18:0), a glycerophospholipid, was found to be correlated with macrophage numbers (r = 0.52, p = 0.039). These metabolites may affect chemokine (such as macrophage chemoattractant protein-1) concentrations in the serum, and ultimately affect pulmonary macrophage recruitment. Our data demonstrated that M. vaccae might alleviate airway inflammation and hyper-responsiveness in asthmatic mice by reversing imbalances in gut microbiota. These novel mechanistic insights are expected to pave the way for novel asthma therapeutic strategies.

Disrupting circadian control of autophagy induces podocyte injury and proteinuria.

The circadian clock influences a wide range of biological process and controls numerous aspects of physiology to adapt to the daily environmental changes caused by Earth's rotation. The kidney clock plays an important role in maintaining tubular function, but its effect on podocytes remains unclear. Here, we found that podocytes expressed CLOCK proteins, and that 2666 glomerular gene transcripts (13.4%), including autophagy related genes, had 24-hour circadian rhythms. Deletion of Clock in podocytes resulted in 1666 gene transcripts with the loss of circadian rhythm including autophagy genes. Podocyte-specific Clock knockout mice at age three and eight months showed deficient autophagy, loss of podocytes and increased albuminuria. Chromatin immunoprecipitation (ChIP) sequence analysis indicated autophagy related genes were targets of CLOCK in podocytes. ChIP-PCR further confirmed Clock binding to the promoter regions of Becn1 and Atg12, two autophagy related genes. Furthermore, the association of CLOCK regulated autophagy with chronic sleep fragmentation and diabetic kidney disease was analyzed. Chronic sleep fragmentation resulted in the loss of glomerular Clock rhythm, inhibition of podocyte autophagy, and proteinuria. Rhythmic oscillations of Clock also disappeared in high glucose treated podocytes and in glomeruli from diabetic mice. Finally, circadian differences in podocyte autophagy were also abolished in diabetic mice. Deletion Clock in podocytes aggravated podocyte injury and proteinuria in diabetic mice. Thus, our findings demonstrate that clock-dependent regulation of autophagy may be essential for podocyte survival. Hence. loss of circadian controlled autophagy may play an important role in podocyte injury and proteinuria.

Epidemiological characteristics and antibody kinetics of elderly population with booster vaccination following both Omicron BA.5 and XBB waves in China.

After the termination of zero-COVID-19 policy, the populace in China has experienced both Omicron BA.5 and XBB waves. Considering the poor antibody responses and severe outcomes observed among the elderly following infection, we conducted a longitudinal investigation to examine the epidemiological characteristics and antibody kinetics among 107 boosted elderly participants following the Omicron BA.5 and XBB waves. We observed that 96 participants (89.7%) were infected with Omicron BA.5, while 59 (55.1%) participants were infected with Omicron XBB. Notably, 52 participants (48.6%) experienced dual infections of both Omicron BA.5 and XBB. The proportion of symptomatic cases appeared to decrease following the XBB wave (18.6%) compared to that after the BA.5 wave (59.3%). Omicron BA.5 breakthrough infection induced lower neutralizing antibody titers against XBB.1.5, BA.2.86, and JN.1, while reinfection with Omicron XBB broadened the antibody responses against all measured Omicron subvariants and may alleviate the wild type-vaccination induced immune imprinting. Boosted vaccination type and comorbidities were the significant factors associated with antibody responses. Updated vaccines based on emerging severe acute respiratory syndrome coronavirus 2 variants are needed to control the Coronavirus Disease 2019 pandemic in the elderly.

Single-cell multiomics reveals increased plasticity, resistant populations, and stem-cell-like blasts in KMT2A-rearranged leukemia.

KMT2A-rearranged (KMT2A-r) infant acute lymphoblastic leukemia (ALL) is a devastating malignancy with a dismal outcome, and younger age at diagnosis is associated with increased risk of relapse. To discover age-specific differences and critical drivers that mediate poor outcome in KMT2A-r ALL, we subjected KMT2A-r leukemias and normal hematopoietic cells from patients of different ages to single-cell multiomics analyses. We uncovered the following critical new insights: leukemia cells from patients <6 months have significantly increased lineage plasticity. Steroid response pathways are downregulated in the most immature blasts from younger patients. We identify a hematopoietic stem and progenitor-like (HSPC-like) population in the blood of younger patients that contains leukemic blasts and form an immunosuppressive signaling circuit with cytotoxic lymphocytes. These observations offer a compelling explanation for the ability of leukemias in young patients to evade chemotherapy and immune-mediated control. Our analysis also revealed preexisting lymphomyeloid primed progenitors and myeloid blasts at initial diagnosis of B-ALL. Tracking of leukemic clones in 2 patients whose leukemia underwent a lineage switch documented the evolution of such clones into frank acute myeloid leukemia (AML). These findings provide critical insights into KMT2A-r ALL and have clinical implications for molecularly targeted and immunotherapy approaches. Beyond infant ALL, our study demonstrates the power of single-cell multiomics to detect tumor intrinsic and extrinsic factors affecting rare but critical subpopulations within a malignant population that ultimately determines patient outcome.

Rotational angle and speed detection via a chip-scale GaN optoelectronic device.

In this paper, a new method for rotational angle and speed measurements is proposed by integrating a GaN optoelectronic chip with a stepped disc. The optoelectronic chip that integrates a light-emitting diode (LED) and a photodiode (PD) is fabricated by wafer-level microfabrication. The disc is designed with a spiral staircase shape, and has increasing thickness distribution along the circumferential direction. The sensing mechanism is that the optoelectronic chip measures angle-dependent intensity change of the light reflected off the stepped disc. Through a series of performance tests, the chip is highly sensitive to a continuous rotation from 0 ∘ to 360 ∘, and produces photocurrent to indicate the rotational angle and speed. A rotational speed up to 5000 rpm is measured with a relative error less than 1.27%. The developed sensing architecture provides an alternative solution for constructing a low-cost, miniaturized, and high-efficiency rotational angle and speed sensing system.

Large-sized light-emitting diode integrated with a thermopile for on-chip temperature and power monitoring.

A large-sized multiple quantum well (MQW) light-emitting diode (LED) integrated with a thermopile for on-chip temperature and power monitoring is presented in this study. Seven thermopile structures, fully compatible with the fabrication of LEDs, are strategically placed at different locations on the LED to monitor its temperature during the operation. Additionally, the thermopile allows for monitoring the power of the LED, as there exists an approximate linear relationship between the light output power and temperature. Compared to traditional methods of measuring LED temperature, the thermopile offers several advantages, including no moving parts, long lifetime, no maintenance, high reliability, and direct conversion without intermediate processes. The results demonstrate that the integration of the thermopiles onto the LED provides superior temperature and power monitoring capabilities. Furthermore, this integrated solution has the potential to enable real-time management and control of LED temperature.

Effect of temperature on GaN-integrated optical transceiver chips.

The gallium nitride (GaN) integrated optical transceiver chip based on multiple quantum wells (MQW) structure exhibits great promise in the fields of communication and sensing. In this Letter, the effect of ambient temperature on the performance of GaN-integrated optical transceiver chips including a blue MQW light-emitting diode (LED) and a MQW photodiode (PD) is comprehensively studied. Temperature-dependent light-emitting and current-voltage characteristics of the blue MQW LEDs are measured with the ambient temperature ranging from -70°C to 120°C. The experimental results reveal a decline in the electroluminescent (EL) intensity and an obvious redshift in the emission peak wavelength of the LED with increasing ambient temperature. The light detection performance of MQW PD under different temperatures is also measured with the illumination of an external blue MQW LED, indicating an enhancement in the PD sensitivity as the temperature rises. Finally, the temperature effect on the MQW PD under the illumination of the MQW LED on the GaN-integrated optical transceiver chip is characterized, and the PD photocurrent increases with higher ambient temperature. Furthermore, the measured temperature characteristics indicate that the GaN-integrated optical transceiver chip offers a promising application potential for optoelectronic temperature sensor.

Collinear optical links based on a GaN-integrated chip for fiber-optic acoustic detection.

This Letter reports a collinear optical interconnect architecture for acoustic sensing via a monolithic integrated GaN optoelectronic chip. The chip is designed with a ring-shaped photodiode (PD) surrounding a light-emitting diode (LED) of a spectral range from 420-530 nm. The axisymmetric structure helps the coaxial propagation of light transmission and reception. By placing this multiple-quantum wells (MQW)-based device and a piece of aluminum-coated polyethylene terephthalate (Al/PET) film on fiber ends, an ultra-compact acoustic sensing system is built. The sound vibrations can be simply detected by direct measurement of the diaphragm deformation-induced power change. An average signal noise ratio (SNR) of 40 dB and a maximum sensitivity of 82 mV/Pa are obtained when the acoustic vibration frequency changes from 400 Hz to 3.2 kHz. This work provides a feasible solution to miniaturize the sensing system footprint and reduce the cost.

R2-ISS staging combined with circulating plasma cells improves risk stratification for newly diagnosed multiple myeloma: a single-center real-world study.

We aimed to evaluate if circulating plasma cells (CPC) detected by flow cytometry could add prognostic value of R2-ISS staging. We collected the electronic medical records of 336 newly diagnosed MM patients (NDMM) in our hospital from January 2017 to June 2023. The median overall survival (OS) for patients and R2-ISS stage I-IV were not reached (NR), NR, 58 months and 53 months, respectively. There was no significant difference in OS between patients with stage I and patients with stage II (P = 0.309) or between patients with stage III and patients with stage IV (P = 0.391). All the cases were re-classified according to R2-ISS stage and CPC numbers ≥ 0.05% (CPC high) or<0.05% (CPC low) into four new risk groups: Group 1: R2-ISS stage I + R2-ISS stage II and CPC low, Group 2: R2-ISS stage II and CPC high + R2-ISS stage III and CPC low, Group 3: R2-ISS stage III and CPC high + R2-ISS stage IV and CPC low, Group 4: R2-ISS stage IV and CPC high. The median OS were NR, NR, 57 months and 32 months. OS of Group 1 was significantly longer than that of Group 2 (P = 0.033). OS in Group 2 was significantly longer than that of Group 3 (P = 0.007). OS in Group 3 was significantly longer than that of Group 4 (P = 0.041). R2-ISS staging combined with CPC can improve risk stratification for NDMM patients.

The optimal ratio of endoscope-sheath diameter with negative-pressure ureteral access sheath: an in vitro research.

PURPOSE: To maintain safe intrarenal pelvic pressure (IPP), the combination of flexible ureteroscope (fURS) and traditional ureteral access sheath (T-UAS) should maintain a basic rule that is the ratio of endoscope-sheath diameter (RESD) ≤ 0.75. However, the negative-pressure ureteral access sheath (NP-UAS) may break the rule of negative pressure suction. This study aimed to examine the effect of NP-UAS on IPP and flow rate (FR) with varying RESD. METHODS: In a 3D-printed renal model, flexible ureteroscopy lithotripsy (fURL) was replicated. Six sizes of fURS paired with 12Fr T-UAS and NP-UAS resulted in six distinct RESDs of 0.63, 0.78, 0.87, 0.89, 0.90, and 0.91. While the irrigation pressure (IRP) was set between 100 and 800 cmH2O and the sucking pressure (SP) was set between 0 and 800 cmH2O, the IPP and FR were measured in each RESD. RESULTS: NP-UASs can reduce the IPP and increase the FR at the same RESD compared to T-UASs. The IPP decreased with increasing SP with NP-UAS. When RESD ≤ 0.78, T-UAS and NP-UAS can maintain IPP < 40 cmH2O in most circumstances. When RESD = 0.87, it is challenging for T-UAS to sustain IPP < 40 cmH2O; however, NP-UAS can do so. When RESD ≥ 0.89, it is difficult to maintain an IPP < 40 cmH2O even with NP-UAS. CONCLUSION: NP-UAS can decrease IPP and increase FR compared with T-UAS. To maintain a safe IPP, it is recommended that RESD < 0.85 when utilizing NP-UAS.

Factors affecting the intraoperative calculi excretion during flexible ureteroscopy lithotripsy: an in vitro analysis.

OBJECTIVE: To explore the parameters influencing intraoperative calculi excretion (ICE) during flexible ureteroscopy lithotripsy (fURL) using in vitro simulation experiments. METHODS: 3D-printed human kidney models were used to simulate the elimination of gravel during fURL. The factors influencing the ICE during fURL were analyzed by comparing the effects of different degrees of hydronephrosis (mild, moderate, and severe), surgical positions (supine and lateral position), ratios of endoscope-sheath diameter (RESD) (0.625, 0.725, and 0.825), gravel sizes (0.50-1.00 mm, 0.25-0.50 mm, and 0.10-0.25 mm), and ureteral access sheaths (UASs) (traditional UAS and negative-pressure UAS) on ICE. RESULTS: The impacts of various UAS, RESD, degree of hydronephrosis, surgical positions, and gravel sizes on ICE were all significant (p < 0.05). We found no evidence of multicollinearity for all the independent variables, and the linear regression equation fitted as ICE ( g / min ) = 0.102 + 0.083 ∗ UAS grade - 0.050 ∗ RESD grade - 0.048 ∗ hydronephrosis grade + 0.065 ∗ position grade - 0.027 ∗ gravel size grade (R2 = 0.569). CONCLUSION: Employing negative-pressure UAS, smaller RESD, milder hydronephrosis, lateral position, and smaller gravel size contribute to improved ICE during fURL. Among them, the adoption of negative-pressure UAS had the most substantial effects.

Model-based precision dosing and remedial dosing recommendations for delayed or missed doses of isoniazid in Chinese patients with tuberculosis.

AIMS: Isoniazid (INH) has been used as a first-line drug to treat tuberculosis (TB) for more than 50 years. However, large interindividual variability was found in its pharmacokinetics, and effects of nonadherence to INH treatment and corresponding remedy regime remain unclear. This study aimed to develop a population pharmacokinetic (PPK) model of INH in Chinese patients with TB to provide model-informed precision dosing and explore appropriate remedial dosing regimens for nonadherent patients. METHODS: In total, 1012 INH observations from 736 TB patients were included. A nonlinear mixed-effects modelling was used to analyse the PPK of INH. Using Monte Carlo simulations to determine optimal dosage regimens and design remedial dosing regimens. RESULTS: A 2-compartmental model, including first-order absorption and elimination with allometric scaling, was found to best describe the PK characteristics of INH. A mixture model was used to characterize dual rates of INH elimination. Estimates of apparent clearance in fast and slow eliminators were 28.0 and 11.2 L/h, respectively. The proportion of fast eliminators in the population was estimated to be 40.5%. Monte Carlo simulations determined optimal dosage regimens for slow and fast eliminators with different body weight. For remedial dosing regimens, the missed dose should be taken as soon as possible when the delay does not exceed 12 h, and an additional dose is not needed. delay for an INH dose exceeds 12 h, the patient only needs to take the next single dose normally. CONCLUSION: PPK modelling and simulation provide valid evidence on the precision dosing and remedial dosing regimen of INH.

Cultivated alien plants with high invasion potential are more likely to be traded online in China.

Biological invasions have become a worldwide problem, and measures to efficiently prevent and control invasions are still in development. Like many other parts of the world, China is undergoing a dramatic increase in plant invasions. Most of the currently 933 established (i.e., naturalized) plant species, of which 214 are categorized as invasive, have been introduced into China for cultivation. It is likely that many of those species are still being traded, particularly online, by plant nurseries. However, studies assessing whether naturalized and invasive species are currently being traded more or less than nonnaturalized aliens are rare. We extracted online-trade information for 13,718 cultivated alien plant taxa on 1688.com, the largest website for domestic B2B in China. We analyzed how the presence in online-nursery catalogs, the number of online nurseries that offerred the species for sale, and the product type (i.e., seeds, live plants and vegetative organs) differed among nonnaturalized, naturalized noninvasive, and invasive species. Compared to nonnaturalized taxa, naturalized noninvasive and invasive taxa were 3.7-5.2 times more likely to be available for purchase. Naturalized noninvasive and invasive taxa were more frequently offered as seeds by online nurseries, whereas nonnaturalized taxa were more frequently offered as live plants. Based on these findings, we propose that, to reduce the further spread of invasive and potentially invasive plants, implementation of plant-trade regulations and a monitoring system of the online horticultural supply chain will be essential.

Cerebral blood flow changes in maintenance hemodialysis patients with restless legs syndrome and their clinical significance:a cross-sectional case-control study.

OBJECTIVE: Restless legs syndrome (RLS) stands as a prevalent neurological complication within maintenance hemodialysis (MHD) patients. However, the alterations in cerebral blood flow (CBF) among MHD-RLS patients remain uncharted. Through the utilization of the arterial spin labeling (ASL) technique, we evaluated the fluctuations in CBF within distinct brain regions and analyzed the risk factors for the development of RLS in MHD patients in the context of the clinic. METHODS: Thirty-one MHD patients with concomitant RLS (MHD-RLS group) and thirty-one non-RLS patients matched based on age, gender, as well as cognitive function (MHD-nRLS group) were included. Through image preprocessing and data analysis, the changes in CBF values in distinct brain regions were obtained, and the CBF values of brain regions with substantial differences between the two groups were correlated with the RLS scores. Furthermore, the differences in baseline data were compared, and through the utilization of multifactorial logistic regression, the independent risk factors for the development of RLS were examined. RESULTS: Compared with the MHD-nRLS group, the MHD-RLS group had increased CBF in the right superior temporal gyrus, reduced CBF in the right hippocampus, left middle frontal gyrus, inferior frontal gyrus of right triangle, middle frontal gyrus of left orbit, left precentral gyrus, and left precuneus. Only left precentral gyrus CBF were negatively correlated with RLS scores after correction for dialysis duration(r = -0.436, P = 0.016). Accordingly, multifactorial regression analysis by stepwise method yielded that the left precentral gyrus CBF values(OR: 0.968, 95%CI: 0.944-0.993, P = 0.012) remained an independent risk factor for RLS in MHD patients. In addition, the results showed that hemodialysis duration (OR: 1.055, 95%CI: 1.014-1.098, P = 0.008) and serum iron levels (OR: 0.685, 95%CI: 0.551-0.852, P = 0.001) were also risk factors for the development of RLS. CONCLUSION: Patients afflicted with MHD-RLS exhibit alterations in CBF across several brain regions. Notably, the left precentral gyrus might serve as a pivotal region influencing the onset of RLS among MHD patients. Furthermore, extended hemodialysis duration and a relative insufficiency in serum iron levels independently contribute as risk factors for RLS development within the MHD patient population.

Tetrandrine alleviates inflammation and promotes macrophage M2 polarization in gouty arthritis by NF-κB-mediated Lcp1.

Gouty arthritis (GA) is an inflammatory disease caused by the deposition of monosodium urate (MSU) crystals into joints. Tetrandrine (TET) is a bisbenzylisoquinoline alkaloid extracted from the root of Stephania tetrandra and can exert an anti-inflammatory function in different diseases. Nevertheless, the specific function of TET in GA remains unclear. We established the GA mouse model by MSU injection into joints of mice. Paw volume and gait score were detected for measuring the degree of joint swelling and the situation of joint dysfunction. Western blot were utilized to test the alterations of M1-related factors (IL-6, IL-1ß, TNF-α, IL-12, and iNOS) and M2-related factors (Mgl1, Mgl2, Pgc1-ß, Arg-1, and IL-10). The activity of NF-κB p65 in tissues was determined. The interaction of NF-κB p65 and Lcp1 was measured by ChIP and luciferase reporter assay. Lcp1 KO mice were utilized to detect the effect of Lcp1 depletion on GA process. TET treatment markedly suppressed MSU-induced joint swelling, joint dysfunction, and joint injury in GA mice. TET can also reduce inflammatory reactions in MUS-induced mice. Furthermore, we proved that TET facilitated M2 macrophage polarization and inhibited M1 macrophage polarization in GA mice. In addition, TET was found to inhibit NF-κB activity and NF-κB-mediated Lcp1 expression. Lcp1 knockdown can improve joint injury and promote M2 macrophage polarization in GA mice, while this effect was further enhanced by TET. TET alleviates inflammation and facilitates macrophage M2 polarization in GA by NF-κB-mediated Lcp1.

A single-center, open label, randomized, controlled study of hydroxychloroquine sulfate in the treatment of low risk PLA2R-associated membranous nephropathy.

OBJECTIVE: To evaluate the efficacy and safety of hydroxychloroquine sulfate (HCQ) in the treatment of low risk phospholipase A2 receptor (PLA2R)-associated membranous nephropathy (MN). METHODS: A total of 110 patients with low risk PLA2R-associated MN were included in the study. Patients who met the inclusion and exclusion criteria were assigned randomly to two groups: the HCQ treatment group and the control group. The control group received standard supportive treatment according to the guidelines, while the HCQ treatment group received HCQ in addition to the supportive treatment. The clinical data of the patients were analyzed, with comparisons made at baseline and during the six-month follow-up period. Any adverse reactions were recorded. RESULTS: The baseline data were comparable between the HCQ treatment group and the control group. At the end of the six-month follow-up period, the reductions in urine protein excretion and serum PLA2R antibody titer were more notable in the HCQ treatment group than those in the control group, with these differences being statistically significant (p < 0.05). Compared to the control group, the HCQ treatment group had fewer patients who were converted from low risk to moderate-to-high risk (p = 0.084). There were also no severe adverse reactions in the HCQ treatment group. CONCLUSION: In patients with low risk PLA2R-associated MN, adequate supportive therapy combined with HCQ is superior to supportive therapy alone in controlling proteinuria and reducing serum PLA2R antibody titers. Additionally, our study demonstrated that the incidence of adverse reactions did not increase. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry (Registration No.: ChiCTR1900021757, Date of registration: 2019-03-08).

Illness Perceptions as a Predictor of Symptom Cluster Trajectories in Patients With Inflammatory Bowel Disease: A Latent Growth Mixture Model.

The aims of this study were to (a) identify the trajectory of symptom clusters in patients with inflammatory bowel disease up to 28 weeks after initiation of infliximab therapy and (b) examine the illness perceptions associated with symptom cluster trajectories. This was a prospective study where participants completed the symptom cluster scale at baseline, 14 weeks, and 28 weeks. A latent growth mixture modeling was used to identify trajectories of symptom clusters that were predicted, using baseline covariates (Brief Illness Perception Questionnaire). A total of 206 patients were included and identified as three latent classes: moderate symptom cluster-stable decline group (C1), high symptom cluster-rapid decline group (C2), and stable symptom cluster-stable trend group (C3). C1 was predicted by cognitive illness perceptions (odds ratio [95% confidence interval]: 1.134 [1.071, 1.200], p < .001). C2 was also predicted by cognitive and emotional illness perceptions (odds ratio [95% confidence interval]: 1.169 [1.095, 1.248], p < .001; odds ratio [95% confidence interval]: 1.174 [1.038, 1.328], p = .011). Patients with inflammatory bowel disease, initiating infliximab therapy, had different symptom cluster trajectories. Illness perceptions were associated with symptom cluster classes, which underline the complexity of symptoms. Paying attention to these factors and providing necessary knowledge and psychological supporting care after infliximab therapy would effectively improve patients' symptom burden.