Miracle-dz/UniFAR-FTUs huggingface dataset:
Self-assembly of kraft lignin into nanospheres in dioxane-water mixtures

Abstract Kraft lignin (KL), a by-product in the pulping and papermaking industry, is an abundant, renewable resource. In this work, nanosphere formation of KL has been investigated via self-assembly induced by adding water to a KL/dioxane solution. The KL nanospheres were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), dynamic light scattering (dynLS) and static light scattering (statLS). It was found that the nanoparticles have uniform nanospherical morphologies, including a small hollow cavity space in the interior. The π-π interactions between the aromatic rings of KL are demonstrated to be an important driving force in the self-assembly process. The KL nanosphere sizes can vary by hundreds of nanometers depending upon the preparation conditions. These newly obtained KL nanospheres have the advantages of biocompatibility, biodegradability, low toxicity, easy preparation, and low cost. Thus KL nanospheres are attractive for applications in life science, medicine, biology, food science, and agriculture. This approach presented here is an economically feasible and facile strategy for the sustainable utilization of kraft lignin.
Comparison of glycemic metrics measured simultaneously by intermittently scanned CGM and real-time CGM in pregnant women with type 1 diabetes.

BACKGROUND We aimed to compare clinically important glycemic metrics with focus on mean sensor glucose and time-below-target range (TBR) during night-time obtained with intermittently scanned CGM (isCGM) and real-time CGM (rtCGM) in early pregnancy in women with type 1 diabetes. METHODS A prospective, observational study including 20 women with type 1 diabetes simultaneously monitored with isCGM (Freestyle Libre, Abbott) and rtCGM (EnvisionTM Pro, Medtronic) for seven days in early pregnancy. Time-in-target range (TIR) was defined as 3.5-7.8 mmol/L. RESULTS Gestational age was median 66 (interquartile range (IQR) 63-74) days and HbA1c was 48 mmol/mol (43-54). Median difference between isCGM and rtCGM was 0.1 mmol/L (-0.1 to 0.5) (p=0.50) and -0.1 mmol/L (-0.4 to 0.2) (p=0.35) for 24 hours and during-night time, respectively . For 24 hours, TBR was 3.9% (1.6-7.0) vs. 2.0% (0.6-3.7) (p=0.06) and TIR was 57.2% (50.8-76.5) vs. 69.6% (55.4-81.5) (p=0.001) for isCGM and rtCGM, respectively. During night-time TBR was 6.5% (0.4-16.7) vs. 0% (0.0-0.8) (p=0.003), TIR was 55.4 (41.1-81.0) vs. 68.8 (52.4-80.3) (p=0.005) and 75% vs. 40% of the women had ≥1 glucose reading below 3.5 mmol/L. CONCLUSIONS In pregnant women with type 1 diabetes, mean sensor glucose was reported similar when measured by isCGM and rtCGM. However, during night-time isCGM measured a clinically relevant higher percentage of TBR compared to rtCGM. Thus, the type of CGM device used may influence adjustments of insulin dose based on the concern for nocturnal hypoglycemia.
Thickness accuracy of virtually designed patient‐specific implants for large neurocranial defects

The combination of computer‐aided design (CAD) techniques based on computed tomography (CT) data to generate patient‐specific implants is in use for decades. However, persisting disadvantages are complicated design procedures and rigid reconstruction protocols, for example, for tailored implants mimicking the patient‐specific thickness distribution of missing cranial bone. In this study we used two different approaches, CAD‐ versus thin‐plate spline (TPS)‐based implants, to reconstruct extensive unilateral and bilateral cranial defects in three clinical cases. We used CT data of three complete human crania that were virtually damaged according to the missing regions in the clinical cases. In total, we carried out 132 virtual reconstructions and quantified accuracy from the original to the generated implant and deviations in the resulting implant thickness as root‐mean‐square error (RMSE). Reconstructions using TPS showed an RMSE of 0.08–0.18 mm in relation to geometric accuracy. CAD‐based implants showed an RMSE of 0.50–1.25 mm. RMSE in relation to implant thickness was between 0.63 and 0.70 mm (TPS) while values for CAD‐based implants were significantly higher (0.63–1.67 mm). While both approaches provide implants showing a high accuracy, the TPS‐based approach additionally provides implants that accurately reproduce the patient‐specific thickness distribution of the affected cranial region.
A rare case of syringocystadenocarcinoma papilliferum of the breast: An institutional retrospective case review and brief literature review

Syringocystadenocarcinoma papilliferum (SCACP) is a rare cutaneous adnexal tumor thought to originate from its benign counterpart, syringocystadenoma papilliferum. These tumors are predominantly located on the head and neck with their location on the breast extraordinarily reported; mammary localization poses a great diagnostic dilemma to the practicing pathologist. Herein, we report an unusual case of an 85‐year‐old woman with an outside diagnosis on a core needle biopsy of metaplastic mammary carcinoma. Upon consultative review of the partial mastectomy specimen, SCACP was identified. Herein, we review SCACP and the diagnostic challenge it poses, especially when localized to the breast. Furthermore, we perform a retrospective review of institutional pathology reports and identified four additional cases of SCACP diagnosed at our institution within the last decade. Finally, we briefly review the literature of SCACP. The entity of SCACP should be well known to pathologists to avoid misdiagnosis.
Dynapenia, abdominal obesity or both: which accelerates the gait speed decline most?

Abstract Objective to investigate whether the combination of dynapenia and abdominal obesity is worse than these two conditions separately regarding gait speed decline over time. Methods a longitudinal study was conducted involving 2,294 individuals aged 60 years or older free of mobility limitation at baseline (gait speed >0.8 m/s) who participated in the English Longitudinal Study of Ageing. Dynapenia was determined as a grip strength <26 kg for men and <16 kg for women. Abdominal obesity was determined as a waist circumference >102 cm for men and >88 cm for women. The participants were divided into four groups: non-dynapenic/non-abdominal obese (ND/NAO); only abdominal obese (AO); only dynapenic (D) and dynapenic/abdominal obese (D/AO). Generalised linear mixed models were used to analyse gait speed decline (m/s) as a function of dynapenia and abdominal obesity status over an 8-year follow-up period. Results over time, only the D/AO individuals had a greater gait speed decline (−0.013 m/s per year, 95% CI: −0.024 to −0.002; P < 0.05) compared to ND/NAO individuals. Neither dynapenia nor abdominal obesity only was associated with gait speed decline. Conclusion dynapenic abdominal obesity is associated with accelerated gait speed decline and is, therefore, an important modifiable condition that should be addressed in clinical practice through aerobic and strength training for the prevention of physical disability in older adults.
Effects of the covid‐19 pandemic on neurological diseases

Covid‐19 has caused many complications for both the infected and those in need of medical care. This may be due to infection‐related prognosis worsening or the patients’ avoidance of referring to the hospital for fear of contracting the infection. The decline of acute referral to the ER of many significant conditions with severe results on both the well‐being and life‐expectancy is a serious concern. To address these concerns, we designed this study to evaluate the recent pandemic's impact on “in‐hospital mortality” caused by neurological disorders pre and postpandemic.
Sustained Tumor Control With MAPK Inhibition in BRAF V600–Mutant Adult Glial and Glioneuronal Tumors

Objective To assess whether RAF and MEK inhibitors (RAFi/MEKi) can provide long-term clinical benefit in adult patients with BRAF V600–mutant glial and glioneuronal tumors (GGNTs), we analyzed tumor response and long-term outcome in a retrospective cohort. Methods We performed a retrospective search in the institutional databases of 6 neuro-oncology departments for adult patients with recurrent or disseminated BRAF V600–mutant GGNTs treated with RAFi/MEKi. Results Twenty-eight adults with recurrent or disseminated BRAF V600–mutant gangliogliomas (n = 9), pleomorphic xanthoastrocytomas (n = 9), and diffuse gliomas (n = 10) were included in the study. At the time that treatment with RAFi/MEKi was started, all tumors displayed radiologic features of high-grade neoplasms. Thirteen patients received RAFi as single agents (vemurafenib [n = 11], dabrafenib [n = 2]), and 15 received combinations of RAFi/MEKi (vemurafenib + cobimetinib [n = 5], dabrafenib + trametinib [n = 10]). Eleven patients achieved a partial or complete response (11 of 28, 39%), with a median reduction of −78% in their tumor burden. Responders experienced a median increase of 10 points in their Karnofsky Performance Status (KPS) score and a median progression-free survival of 18 months, which was longer than achieved with first-line treatment (i.e., 7 months, p = 0.047). Responders had better KPS score (p = 0.018) and tended to be younger (p = 0.061) and to be treated earlier (p = 0.099) compared to nonresponders. Five patients were rechallenged with RAFi/MEKi at progression, with novel tumor responses in 2. On univariate and multivariate analyses, response to RAFi/MEKi was an independent predictor of overall survival. Conclusions Our study highlights the long-term clinical benefits of RAFi/MEKi in adult patients with BRAF V600–mutant GGNTs and encourages rechallenge in responders. Classification of Evidence This study provides Class III evidence that, for adult patients with BRAF V600-mutant GGNT, RAFi/MEKi can reduce tumor burden and provide clinical benefit.
Neuromodulatory effects of repetitive transcranial magnetic stimulation on neural plasticity and motor functions in rats with an incomplete spinal cord injury: A preliminary study

We investigated the effects of intermittent theta-burst stimulation (iTBS) on locomotor function, motor plasticity, and axonal regeneration in an animal model of incomplete spinal cord injury (SCI). Aneurysm clips with different compression forces were applied extradurally around the spinal cord at T10. Motor plasticity was evaluated by examining the motor evoked potentials (MEPs). Long-term iTBS treatment was given at the post-SCI 5th week and continued for 2 weeks (5 consecutive days/week). Time-course changes in locomotor function and the axonal regeneration level were measured by the Basso Beattie Bresnahan (BBB) scale, and growth-associated protein (GAP)-43 expression was detected in brain and spinal cord tissues. iTBS-induced potentiation was reduced at post-1-week SCI lesion and had recovered by 4 weeks post-SCI lesion, except in the severe group. Multiple sessions of iTBS treatment enhanced the motor plasticity in all SCI rats. The locomotor function revealed no significant changes between pre- and post-iTBS treatment in SCI rats. The GAP-43 expression level in the spinal cord increased following 2 weeks of iTBS treatment compared to the sham-treatment group. This preclinical model may provide a translational platform to further investigate therapeutic mechanisms of transcranial magnetic stimulation and enhance the possibility of the potential use of TMS with the iTBS scheme for treating SCIs.
Permitted daily exposure limits for noteworthy N‐nitrosamines

A genotoxic carcinogen, N‐nitrosodimethylamine (NDMA), was detected as a synthesis impurity in some valsartan drugs in 2018, and other N‐nitrosamines, such as N‐nitrosodiethylamine (NDEA), were later detected in other sartan products. N‐nitrosamines are pro‐mutagens that can react with DNA following metabolism to produce DNA adducts, such as O6‐alkyl‐guanine. The adducts can result in DNA replication miscoding errors leading to GC>AT mutations and increased risk of genomic instability and carcinogenesis. Both NDMA and NDEA are known rodent carcinogens in male and female rats. The DNA repair enzyme, methylguanine DNA‐methyltransferase can restore DNA integrity via the removal of alkyl groups from guanine in an error‐free fashion and this can result in nonlinear dose responses and a point of departure or “practical threshold” for mutation at low doses of exposure. Following International recommendations (ICHM7; ICHQ3C and ICHQ3D), we calculated permissible daily exposures (PDE) for NDMA and NDEA using published rodent cancer bioassay and in vivo mutagenicity data to determine benchmark dose values and define points of departure and adjusted with appropriate uncertainty factors (UFs). PDEs for NDMA were 6.2 and 0.6 μg/person/day for cancer and mutation, respectively, and for NDEA, 2.2 and 0.04 μg/person/day. Both PDEs are higher than the acceptable daily intake values (96 ng for NDMA and 26.5 ng for NDEA) calculated by regulatory authorities using simple linear extrapolation from carcinogenicity data. These PDE calculations using a bench‐mark approach provide a more robust assessment of exposure limits compared with simple linear extrapolations and can better inform risk to patients exposed to the contaminated sartans.
Chronic heat stress delays immune system development and alters serotonin signaling in pre-weaned dairy calves

Exposure to heat stress can alter the development and immune system function in dairy calves. Serotonin is an immunomodulatory biogenic amine that functions as a neurotransmitter and as a stress-response mediator. Our objectives were to characterize the patterns of serum serotonin concentrations and the pattern of serotonin-related genes expressed by immune cells of calves exposed to chronic heat stress or heat stress abatement during early life, and to explore whether these might relate to immune system development. Dairy calves were exposed to chronic heat stress (HS; n = 6) or heat stress abatement (cooling, CL; n = 6) across the prenatal (late gestation, last 46 d) and postnatal (from birth to weaning, 56 d) developmental windows. Blood samples were collected to harvest serum (weekly, from d 1 to 49), to isolate of circulating leukocyte mRNA (at 1, 21 and 42 d of age) and characterize immune cell populations by flow cytometry (at 21 and 47 d of age). Calves exposed to chronic heat stress pre- and postnatally had lower red blood cell counts and lower circulating serotonin, immunoglobulin G, and B-lymphocytes compared to CL calves. Circulating blood leukocyte mRNA expression of serotonin receptors -1A, -1F, -4 and -5 was greater, while heat shock protein 70 and immune-related genes (i.e., TBX21, TLR4, and TGFβ) were lower in HS relative to CL calves. Peripheral blood leukocytes from all calves secreted serotonin and interleukin-6 after in-vitro lipopolysaccharide stimulation. However, the HS calves produced more serotonin and less interleukin-6 than CL calves when activated in-vitro. Together, our data suggest that providing heat stress abatement to dairy calves across prenatal and postnatal developmental windows might modulate the serotonin synthesis pathway in ways that may benefit humoral immunity against microbial pathogens.
The mechanism of action of the SSB interactome reveals it is the first OB‐fold family of genome guardians in prokaryotes

The single‐stranded DNA binding protein (SSB) is essential to all aspects of DNA metabolism in bacteria. This protein performs two distinct, but closely intertwined and indispensable functions in the cell. SSB binds to single‐stranded DNA (ssDNA) and at least 20 partner proteins resulting in their regulation. These partners comprise a family of genome guardians known as the SSB interactome. Essential to interactome regulation is the linker/OB‐fold network of interactions. This network of interactions forms when one or more PXXP motifs in the linker of SSB bind to an OB‐fold in a partner, with interactome members involved in competitive binding between the linker and ssDNA to their OB‐fold. Consequently, when linker‐binding occurs to an OB‐fold in an interactome partner, proteins are loaded onto the DNA. When linker/OB‐fold interactions occur between SSB tetramers, cooperative ssDNA‐binding results, producing a multi‐tetrameric complex that rapidly protects the ssDNA. Within this SSB‐ssDNA complex, there is an extensive and dynamic network of linker/OB‐fold interactions that involves multiple tetramers bound contiguously along the ssDNA lattice. The dynamic behavior of these tetramers which includes binding mode changes, sliding as well as DNA wrapping/unwrapping events, are likely coupled to the formation and disruption of linker/OB‐fold interactions. This behavior is essential to facilitating downstream DNA processing events. As OB‐folds are critical to the essence of the linker/OB‐fold network of interactions, and they are found in multiple interactome partners, the SSB interactome is classified as the first family of prokaryotic, oligosaccharide/oligonucleotide binding fold (OB‐fold) genome guardians.
Yunmen (LU 2) combined with neck-seven-acupoint acupuncture for arm numbness caused by cervical spondylotic radiculopathy

Abstract Rationale: Cervical spondylotic radiculopathy (CSR) is a common sensory, motor, and reflex disorder. Numbness, a common subjective symptom of CSR, lacks objective quantitative indicators and recognized effective treatments, but is also difficult to recover from. We present a case report describing a traditional acupuncture treatment for CSR, utilizing a special acupuncture method and point, namely the Yunmen point. Patient concerns: A 40-year-old woman presented with unilateral arm numbness caused by CSR. Diagnoses: A diagnosis of CSR was made in the orthopedic department of a local hospital. Interventions: We attempted acupuncture at the Yunmen (LU 2) acupoint combined with neck-seven-acupoint under computed tomographic guidance. Outcomes: After 10 times treatment sessions, the patient no longer experienced weakness, coldness, or numbness in the affected upper limb. In addition, the stiffness in the neck and shoulders was reduced. On physical examination, the patient's left brachial plexus traction test was negative; reassessment of the CSR-20-point score scale showed a perfect score, and the visual analog scale score was 0. Lessons: Our report indicates that acupuncture at the LU 2 acupoint combined with neck-seven-acupoint is effective in treating numbness and coldness of the arm, and other neurological symptoms caused by cervical spondylosis. Moreover, with the appropriate acupuncture technique, the risk of acupuncture at the LU 2 acupoint can be minimized.
Meteorological factors against COVID-19 and the role of human mobility

In the vein of recent empirical literature, we reassessed the impact of weather factors on Covid-19 daily cases and fatalities in a panel of 37 OECD countries between 1st January and 27th July 2020. We considered five different meteorological factors. For the first time, we used a dynamic panel model and considered two different kinds of channels between climate and Covid-19 virus: direct/physical factors related to the survival and durability dynamics of the virus on surfaces and outdoors and indirect/social factors through human behaviour and individual mobility, such as walking or driving outdoors, to capture the impact of weather on social distancing and, thus, on Covid-19 cases and fatalities. Our work revealed that temperature, humidity and solar radiation, which has been clearly under considered in previous studies, significantly reduce the number of Covid-19 cases and fatalities. Indirect effects through human behaviour, i.e., correlations between temperature (or solar radiation) and human mobility, were significantly positive and should be considered to correctly assess the effects of climatic factors. Increasing temperature, humidity or solar radiation effects were positively correlated with increasing mobility effects on Covid-19 cases and fatalities. The net effect from weather on the Covid-19 outbreak will, thus, be the result of the physical/direct negative effect of temperature or solar radiation and the mobility/indirect positive effect due to the interaction between human mobility and those meterological variables. Reducing direct effects of temperature and solar radiation on Covid-19 cases and fatalities, when they were significant, were partly and slightly compensated for positive indirect effects through human mobility. Suitable control policies should be implemented to control mobility and social distancing even when the weather is favourable to reduce the spread of the Covid-19 virus.
Imaging flow cytometry and fluorescence microscopy in assessing radiation response in lymphocytes from umbilical cord blood and cancer patients

DNA double strand breaks (DSB) induced by ionizing radiation (IR) are usually measured using γH2AX/53BP1 DNA repair foci, that is considered to be the most sensitive assay for DSB analysis. While fluorescence microscopy (FM) is the gold standard for this analysis, imaging flow cytometry (IFC) may offer number of advantages such as lack of the fluorescence background, higher number of cells analyzed, and higher sensitivity in detection of DNA damage induced by IR at low doses. Along with appearance of γH2AX foci, the variable fraction of the cells exhibits homogeneously stained γH2AX signal resulting in so‐called γH2AX pan‐staining, which is believed to appear at early stages of apoptosis. Here, we investigated incidence of γH2AX pan‐staining at different time points after irradiation with γ‐rays using IFC and compared the obtained data with the data from FM. Appearance of γH2AX pan‐staining during the apoptotic process was further analyzed by fluorescence‐activated cell sorting (FACS) of cells at different stages of apoptosis and subsequent immunofluorescence analysis. Our results show that IFC was able to reveal dose dependence of pan‐staining, while FM failed to detect all pan‐staining cells. Moreover, we found that γH2AX pan‐staining could be induced by therapeutic, but not low doses of γ‐rays and correlate well with percentage of apoptotic cells was analyzed using flow cytometric Annexin‐V/7‐AAD assay. Further investigations showed that γH2AX pan‐staining is formed in the early phases of apoptosis and remains until later stages of apoptotic process. Apoptotic DNA fragmentation as detected with comet assay using FM correlated with the percentage of live and late apoptotic/necrotic cells as analyzed by flow cytometry. Lastly, we successfully tested IFC for detection of γH2AX pan‐staining and γH2AX/53BP1 DNA repair foci in lymphocyte of breast cancer patients after radiotherapy, which may be useful for assessing individual radiosensitivity in a clinically relevant cohort of patients.
Colorectal cancer screening and surveillance strategy for patients with Diamond Blackfan anemia: Preliminary recommendations from the Diamond Blackfan Anemia Registry

Diamond Blackfan anemia (DBA) is a rare inherited bone marrow failure syndrome characterized by red cell failure, congenital anomalies, poor linear growth, and cancer predisposition. Two previous analyses from the Diamond Blackfan Anemia Registry have quantified DBA as a cancer predisposition syndrome of moderate cancer penetrance. Patients with DBA have a 4.8‐fold higher relative risk of developing cancer with an overall cumulative incidence of 13.7% by age 45 years. The two most prevalent solid tumors are colorectal cancer (CRC) and osteogenic sarcoma. Current and evolving data support the institution of cancer screening and surveillance strategies for CRC in DBA.