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Abstract The discovery of efficient magnetization switching upon device activation by spin Hall effect (SHE)-induced spin–orbit torque (SOT) changed the course of magnetic random-access memory (MRAM) research and development. However, for electronic systems with perpendicular magnetic anisotropy (PMA), the use of SOT is still hampered by the necessity of a longitudinal magnetic field to break magnetic symmetry and achieve deterministic switching. In this work, we demonstrate that robust and tunable field-free current-driven SOT switching of perpendicular magnetization can be controlled by the growth protocol in Pt-based magnetic heterostructures. We further elucidate that such growth-dependent symmetry breaking originates from the laterally tilted magnetic anisotropy of the ferromagnetic layer with PMA, a phenomenon that has been largely neglected in previous studies. We show experimentally and in simulation that in a PMA system with tilted anisotropy, the deterministic field-free switching exhibits a conventional SHE-induced damping-like torque feature, and the resulting current-induced effective field shows a nonlinear dependence on the applied current density. This relationship could be potentially misattributed to an unconventional SOT origin.

To make spin–orbit torque magnetic random access memory (SOT-MRAM) practical, current-induced magnetization switching without an external bias field is essential. Given that the CoFeB/MgO structure has already been used in typical spin-transfer torque-MRAM for its high tunneling magnetoresistance, leveraging a similar material system to achieve field-free SOT switching is of great importance. In this work, we systematically investigate the field-free switching mechanism in CoFeB/W/CoFeB T-type structures, where the two CoFeB layers are in-plane and perpendicularly magnetized, respectively. Initial SOT characterization shows a sizable zero-field SOT efficacy (χHx=0) for such T-type devices. Furthermore, field-free angle-dependent SOT measurement confirms the parallel relationship between the built-in bias field and the magnetization of the in-plane magnetized CoFeB. Based on thorough verification and exclusion of other potential mechanisms, the Néel orange-peel effect emerges as the dominant origin for such a built-in bias field, where a positive correlation between the deposited film surface roughness and χHx=0 is found. Based on this discovery, the field-free switching efficacy in T-type structures is further optimized via film roughness tuning and examined with pillar-shaped devices. Our results provide insights into the tentative approach to improve field-free switching using T-type devices and the feasibility of downscaling.

Middle East respiratory syndrome (MERS) is a viral respiratory disease caused by a de novo coronavirus—MERS-CoV—that is associated with high mortality. However, the mechanism by which MERS-CoV infects humans remains unclear. To date, there is no effective vaccine or antibody for human immunity and treatment, other than the safety and tolerability of the fully human polyclonal Immunoglobulin G (IgG) antibody (SAB-301) as a putative therapeutic agent specific for MERS. Although rapid diagnostic and public health measures are currently being implemented, new cases of MERS-CoV infection are still being reported. Therefore, various effective measures should be taken to prevent the serious impact of similar epidemics in the future. Further investigation of the epidemiology and pathogenesis of the virus, as well as the development of effective therapeutic and prophylactic anti-MERS-CoV infections, is necessary. For this purpose, detailed information on MERS-CoV proteins is needed. In this review, we describe the major structural and nonstructural proteins of MERS-CoV and summarize different potential strategies for limiting the outbreak of MERS-CoV. The combination of computational biology and virology can accelerate the advanced design and development of effective peptide therapeutics against MERS-CoV. In summary, this review provides important information about the progress of the elimination of MERS, from prevention to treatment. Keywords: MERS-CoV, Spike protein, Structural protein, Accessory protein, Nonstructural protein

Abstract Background Antibody-drug conjugates (ADCs) targeting the RON receptor, a tumorigenic factor contributing to cancer malignancy, has been considered as a novel strategy for cancer therapy. Here we describe a humanized antibody recognizing the RON plexin-semaphorin-integrin (PSI) domain with increased drug delivery capability for potential clinical application. Method Monoclonal antibody PCM5B14 specific to the human and monkey RON PSI domain was generated and characterized by various immunological methods. Humanized antibody H5B14 was created by grafting PCM5B14 complementarity-determining regions into human IgG1/κ acceptor frameworks and conjugated with monomethyl auristatin E and duocarmycin to form two H5B14-based ADCs. Stability of H5B14-based ADCs in human plasma was measured using hydrophobic interaction chromatography. Various biochemical and biological assays were used to determine ADC- regulated RON internalization, cell viability, spheroid formation, and death of cancer stem-like cells. Efficacies of H5B14-based ADCs in vivo were validated using tumor xenograft models. Maximal tolerated doses of H5B14-based ADCs were established in mice. Results H5B14 was highly specific to the human RON PSI domain and superior over other anti-RON ADCs in induction of RON internalization in various cancer cell lines tested. H5B14-based ADCS had a drug to antibody ratio of ~ 3.70:1 and were stable in human plasma with a minimal dissociation within a 10-day period. Functionally, H5B14-mediated drug delivery decreased cell viability at early stages with an average IC50 at ~ 20 nM in multiple cancer cell lines examined. H5B14-based ADCs also inhibited spheroid formation and caused death of cancer stem-like cells with RON+/CD44+/ESA+ phenotypes. In vivo, H5B14-based ADCs in a single injection inhibited tumor xenograft growth mediated by multiple cancer cell lines. Tumoristatic concentrations calculated from xenograft tumor models were in the range of 0.63 to 2.0 mg/kg bodyweight. Significantly, H5B14-based ADCs were capable of eradicating tumors at variable levels across multiple xenograft models regardless their malignant statuses. Toxicologically, H5B14-based ADCs were well tolerated in mice up to 60 mg/kg. Conclusion H5B14-based ADCs targeting the RON PSI domain are superior in inducing RON internalization, leading to robust drug delivery and overall inhibition and eradication of tumors in multiple xenograft models. These findings warrant H5B14-based ADCs for clinical trials in the future.

Abstract Background Aberrant expression of the RON receptor tyrosine kinase is a pathogenic feature and a validated drug target in various types of cancers. Currently, therapeutic antibodies targeting RON for cancer therapy are under intensive evaluation. Here we report the development and validation of a novel humanized anti-RON antibody-drug conjugate for cancer therapy. Methods Antibody humanization was achieved by grafting sequences of complementarity-determining regions from mouse monoclonal antibody Zt/g4 into human IgG1/κ acceptor frameworks. The selected humanized Zt/g4 subclone H1L3 was conjugated with monomethyl auristatin E using a dipeptide linker to form H-Zt/g4-MMAE. Pharmacokinetic analysis of H-Zt/g4-MMAE was determined using hydrophobic interaction chromatography and a MMAE ADC ELISA kit. Biochemical and biological assays were used for measuring RON expression, internalization, cell viability and death. Therapeutic efficacies of H-Zt/g4-MMAE were validated in vivo using three pancreatic cancer xenograft models. Toxicological activities of H-Zt/g4-MMAE were determined in mouse and cynomolgus monkey. Results H-Zt/g4-MMAE had a drug to antibody ratio of 3.77:1 and was highly stable in human plasma with a dissociation rate less than 5% within a 20 day period. H-Zt/g4-MMAE displayed a favorable pharmacokinetic profile in both mouse and cynomolgus monkey. In vitro, H-Zt/g4-MMAE induced RON internalization, which results in killing of pancreatic cancer cells with IC50 values at 10–20 nM. In vivo, H-Zt/g4-MMAE inhibited pancreatic cancer xenograft growth with tumoristatic concentrations at 1~3 mg/kg bodyweight. Significantly, H-Zt/g4-MMAE eradicated tumors across multiple xenograft models regardless their chemoresistant and metastatic statuses. Moreover, H-Zt/g4-MMAE inhibited and eradicated xenografts mediated by pancreatic cancer stem-like cells and by primary cells from patient-derived tumors. Toxicologically, H-Zt/g4-MMAE is well tolerated in mice up to 60 mg/kg. In cynomolgus monkey, H-Zt/g4-MMAE up to 30 mg/kg had a manageable and reversible toxicity profile. Conclusions H-Zt/g4-MMAE is superior in eradication of pancreatic cancer xenografts with favorable pharmacokinetic profiles and manageable toxicological activities. These findings warrant the transition of H-Zt/g4-MMAE into clinical trials in the future.

Background/Aims: Monoclonal antibodies (mAbs) are presently the most promising treatment against Ebola virus disease (EVD), and cocktail of two or more antibodies likely confers protection through complementary mechanisms. Zaire Ebolavirus (EBOV) glycoprotein (GP) and viral protein 40 (VP40) are targets for designing neutralizing antibodies. Currently, the antiviral therapeutics of mAb-cocktails are still limited solely to anti-GP antibodies，there is no Abs cocktail against Zaire EBOV GP and VP40, which both have important interactions with host cellular membrane. Methods: We used hybridoma technology to produce anti-Zaire EBOV GP mAb against GP receptor binding domain, and anti-Zaire EBOV VP40 mAbs against the N-terminal domain, the C-terminal domain, respectively; synthesized Zaire EBOV transcription and replication competent virus like particles (trVLPs), which model even all aspects of the EBOV life cycles in order to evaluate the anti-viral effect of mAbs. Then, we characterized the anti- Zaire EBOV trVLPs effect of anti-GP and VP40 mAbs in vitro by real time-PCR, immunofluorescence assay and western blot analysis. Results: Our results demonstrate that anti-GP or anti-VP40 mAbs effectively inhibit trVLPs replication. The cocktails of anti-GP and anti-VP40 mAbs, or between anti-VP40 mAbs, had synergistic anti-trVLPs effect. Meanwhile, the detailed DNA and amino acid sequences of the mAbs were checked. Conclusion: The study verifies neutralizing efficacy of anti-GP or anti-VP40 mAb, report promising cocktail of anti-GP and anti-VP40 mAb, or cocktail of two anti-VP40 mAbs. To our knowledge, this is the first account to report the important anti-viral effect of cocktails of anti-GP and anti-VP40 mAbs in vitro.

Background/Aims: Since the first case of novel H7N9 infection was reported, China has experienced five epidemics of H7N9. During the fifth wave, a highly pathogenic H7N9 strain emerged. In order to assess whether the H7N9 vaccine based on A/Zhejiang/DTID-ZJU01/2013(H7N9) was effective in protecting against highly pathogenic H7N9, we conducted this study. Methods: Groups of mice were immunized twice by intraperitoneal injection with 500 µl of either split vaccine alone or MF59-adjuvanted vaccine. Serum was collected 2 weeks after the second vaccine booster. The hemagglutinin inhibition test was conducted on vaccine seed and highly pathogenic H7N9 to evaluate the neutralization of highly pathogenic H7N9. We also immunized mice and challenged them with highly pathogenic H7N9. Mice were observed for illness, weight loss, and death at 1 week and 2 weeks post-infection. Then, the mice were sacrificed and lungs were removed. Antibody responses were assessed and pathological changes in the lung tissue were evaluated. Results: The ability of serum to neutralize highly pathogenic H7N9 was reduced. In mice, highly pathogenic H7N9 was more virulent than A/Zhejiang/DTID-ZJU01/2013(H7N9). After challenge with highly pathogenic H7N9, all mice died while mice challenged with A/Zhejiang/DTID-ZJU01/2013(H7N9) all recovered. The A/ZJU01/PR8/2013 split H7N9 avian influenza vaccine was able to protect against infection with highly pathogenic H7N9 in mice, with or without MF59. Moreover, H7N9 vaccine adjuvanted with MF59 produced high antibody levels, which lead to better protection. Conclusions: The A/ZJU01/PR8/2013 split H7N9 avian influenza vaccine based on A/Zhejiang/DTID-ZJU01/2013(H7N9) is effective in protecting against highly pathogenic H7N9. H7N9 vaccine adjuvanted with MF59 offers better protection against infection with highly pathogenic H7N9. In order to make the H7N9 vaccine applicable to humans, further clinical trials are required to evaluate MF59 adjuvanted vaccine. Meanwhile, the vaccine strain should be updated based on the highly pathogenic H7N9 gene sequence.

RON (recepteur d'origine nantais) and MET (hepatocyte growth factor receptor) are tyrosine kinase receptors. Various cancers have aberrant RON and MET expression and activation, which contribute to cancer cell proliferation, invasiveness, and metastasis. Here, we explored RON and MET expression in pancreatic cancer and their relationship with overall survival (OS) time, and evaluated their significance as therapeutic targets of tyrosine kinase inhibitors in pancreatic cancer. We enrolled 227 patients with pancreatic cancer in the study. RON and MET expression was analyzed by immunohistochemical staining. Four human pancreatic cancer cell lines expressing variable levels of RON or MET and four MET superfamily inhibitors (BMS777607, PHA665752, INCB28060, Tivantinib) were used. The effect of the four tyrosine kinase inhibitors on cell viability, migration, and apoptosis were determined using cell viability, scratch wound healing, and Caspase-Glo 3/7 assays. Cellular signaling was analyzed by immunoprecipitation and western blotting. The therapeutic efficacy of the tyrosine kinase inhibitors was determined with mouse xenograft pancreatic cancer models in vivo. There was wide aberrant RON and MET expression in the cancer tissues. In 227 pancreatic cancer samples, 33% had RON overexpression, 41% had MET overexpression, and 15.4% had RON and MET co-overexpression. RON and MET expression were highly correlated. RON and MET expression levels were significantly related to OS. Patients with RON and MET co-overexpression had poorer OS. BMS777607 and PHA665752 inhibited pancreatic cancer cell viability and migration, and promoted apoptosis by inhibiting RON and MET phosphorylation and further inhibiting the downstream signaling pathways in vitro. They also inhibited tumor growth and further inhibited phosphorylated (phosphor)-RON and phospho-MET expression in the mouse xenograft models in vivo effectively. INCB28060, which inhibits the MET signaling pathway alone, was not effective. RON and MET can be important indicators of prognosis in pancreatic cancer. Tyrosine kinase inhibitors targeting RON and MET in pancreatic cancer are a novel and potential approach for pancreatic cancer therapy.

Ebolavirus (EBOV) life cycle involves interactions with numerous host factors, but it remains poorly understood, as does pathogenesis. Herein, we synthesized 65 siRNAs targeting host genes mostly connected with aspects of the negative-sense RNA virus life cycle (including viral entry, uncoating, fusion, replication, assembly, and budding). We produced EBOV transcription- and replication-competent virus-like particles (trVLPs) to mimic the EBOV life cycle. After screening host factors associated with the trVLP life cycle, we assessed interactions of host proteins with trVLP glycoprotein (GP), VP40, and RNA by co-immunoprecipitation (Co-IP) and chromatin immunoprecipitation (ChIP). The results demonstrate that RNAi silencing with 11 siRNAs (ANXA5, ARFGAP1, FLT4, GRP78, HSPA1A, HSP90AB1, HSPA8, MAPK11, MEK2, NTRK1, and YWHAZ) decreased the replication efficiency of trVLPs. Co-IP revealed nine candidate host proteins (FLT4, GRP78, HSPA1A, HSP90AB1, HSPA8, MAPK11, MEK2, NTRK1, and YWHAZ) potentially interacting with trVLP GP, and four (ANXA5, GRP78, HSPA1A, and HSP90AB1) potentially interacting with trVLP VP40. Ch-IP identified nine candidate host proteins (ANXA5, ARFGAP1, FLT4, GRP78, HSPA1A, HSP90AB1, MAPK11, MEK2, and NTRK1) interacting with trVLP RNA. This study was based on trVLP and could not replace live ebolavirus entirely; in particular, the interaction between trVLP RNA and host proteins cannot be assumed to be identical in live virus. However, the results provide valuable information for further studies and deepen our understanding of essential host factors involved in the EBOV life cycle.

Following publication of the original article [1], the author reported two errors in the authors affiliations:

Abstract In dairy farming, the uncertainty of cow calving date often imposes waiting costs for days on farmers. Improving the accuracy of calving date prediction would mitigate these costs, specifically before a few days of the event. We monitored and analyzed the heart rate patterns of eight pregnant cows in the days leading up to calving using a dedicated monitoring device. We decomposed the heart rate data into three distinct components: trend, daily cycle, and the remainder, and discovered that the heart rate trend exhibited a sharp decline more than 40 h before the calving event via the trend turning point. To detect the turning point, we applied common financial technical indicators traditionally used to identify turning points of asset prices in trading markets for the extracted heart rate trend. This study remains a feasibility study because of the limited observations, but it indicates that these indicators can effectively capture the trend’s turning point in real time, offering a promising approach for enhanced calving prediction. In addition to discussing the practical implications for cow management, we also contemplate the broader utility of these technical indicators in the context of various dynamic scientific data analyses.

Objective Parturition is crucial for dams, their calves, and cow managers. The prediction of calving time, which assists cow managers to decide on the relocation of cows to maternity pens and necessity of human supervision, is a pivotal aspect of livestock farming. However, existing methods of predicting calving time in dairy cows based on hormonal changes and clinical symptoms are time-consuming and yield unreliable predictions. Accordingly, we investigated whether heart rate variability (HRV) which is a non-invasive assessment of autonomic nervous system (ANS) activity and behavior during the prepartum period would be useful for predicting calving time in dairy cows. Methods Eight pregnant cows were surveilled under electrocardiogram and video recordings for HRV and behavioral analyses, respectively. HRV parameters in time and frequency domains were evaluated. A 24-h time budget was calculated for each of six types of behavior (standing and lying with or without rumination, sleeping, and eating). Results Heart rate on calving day is considerably higher than those recorded on the days preceding calving. Low frequency power declined, whereas high frequency power escalated on the calving day compared to the period between 24 and 48 h before calving. The time budget for ruminating while lying decreased and that while standing increased markedly on the calving day compared to those allocated on the preceding days; nonetheless, the total time budget for ruminating did not differ during the prepartum period. Conclusion We elucidated the ANS activity and behavioral profiles during prepartum period. Our results confirm that HRV parameters and behavior are useful for predicting calving time, and interestingly indicate that the time budget for ruminating while standing (or lying) may serve as a valuable predictor of calving. Collectively, our findings lay the foundation for future investigations to determine other potential predictors and formulate an algorithm for predicting calving time.

Background Pulmonary hypertension (PH) is highly prevalent in patients with heart failure with preserved ejection fraction (HFpEF), and it is a strong predictor of adverse outcomes. We aimed to determine possible echocardiographic parameters to predict the presence of PH in patients with HFpEF Methods and Results A total of 113 patients with HFpEF were prospectively enrolled from November 2017 to July 2022. The patients underwent invasive cardiac catheterization and simultaneous echocardiography at rest and during exercise. The parameters indicating right ventricle‐pulmonary artery uncoupling, including tricuspid annular plane systolic excursion (TAPSE)/pulmonary artery systolic pressure (PASP) and tricuspid annular systolic velocity (TAS’)/PASP were calculated. Receiver operating characteristic curve analysis was used to determine the optimal cut‐off points of TAPSE/PASP and TAS’/PASP to differentiate patients with HFpEF with PH from those without PH. Sixty‐eight patients with HFpEF with PH and 45 without PH were included. Those with PH had lower TAPSE/PASP and TAS’/PASP at rest and during exercise compared with those without PH. Both resting/stress TAPSE/PASP and TAS’/PASP were correlated with rest/exercise pulmonary capillary wedge pressure and mean pulmonary artery pressure. In multivariable regression analysis, TAPSE/PASP remained a significant predictor of exercise pulmonary capillary wedge pressure and mean pulmonary artery pressure. In receiver operating characteristic curve analysis, the optimal cut‐off points of TAPSE/PASP and TAS’/PASP to differentiate patients with HFpEF with PH from those without PH were ≤0.62 and ≤0.47, respectively. Conclusions Right ventricle‐pulmonary artery uncoupling is closely correlated with abnormal rest/exercise hemodynamics (pulmonary capillary wedge pressure and mean pulmonary artery pressure) in patients with HFpEF. TAPSE/PASP and TAS’/PASP can be useful parameters to detect PH in patients with HFpEF.

The paraspinal muscles of the cervical, thoracic, and lumbar spine are important pain generators because muscle strains or myofascial pain syndrome caused by trigger points are common during clinical practice. Ultrasonography is the most convenient imaging tool for evaluating these muscles due to its advantages, such as providing good delineation of soft tissues, easy accessibility, and zero radiation. Additionally, ultrasound can serve as a useful guiding tool for paraspinal muscle intervention to prevent inadvertent injuries to vital axial neurovascular structures. This pictorial essay presents ultrasound scanning protocols for the paraspinal and other associated muscles as well as a discussion of their clinical relevance. Axial magnetic resonance imaging has also been used to elucidate reciprocal anatomy. In conclusion, ultrasound imaging proves to be a valuable tool that facilitates the differentiation of individual paraspinal muscles. This capability significantly enhances the precision of interventions designed to address myofascial pain syndrome.

Purpose: Triple-negative breast cancer (TNBC) is highly malignant and has poor prognosis and a high mortality rate. The lack of effective therapy has spurred our investigation of new targets for treating this malignant cancer. Here, we identified RON (macrophage-stimulating 1 receptor) and MET (MET proto-oncogene, receptor tyrosine kinase) as a prognostic biomarker and therapeutic targets for potential TNBC treatment. Materials and Methods: We analyzed RON and MET expression in 187 primary TNBC clinical samples with immunohistochemistry. We validated the targeted therapeutic effects of RON and MET in TNBC using three tyrosine kinase inhibitors (TKIs): BMS-777607, INCB28060, and tivantinib. The preclinical therapeutic efficacy of the TKIs was mainly estimated using a TNBC xenograft model. Results: Patients with TNBC had widespread, abnormal expression of RON and MET. There was RON overexpression, MET overexpression, and RON and MET co-overexpression in 63 (33.7%), 63 (33.7%), and 43 cases (23.0%), respectively, which had poor prognosis and short survival. In vivo, the TKI targeting RON ant MET inhibited the activation of the downstream signaling molecules, inhibited TNBC cell migration and proliferation, and increased TNBC cell apoptosis; in the xenograft model, they significantly inhibited tumor growth and shrank tumor volumes. The TKI targeting RON and Met, such as BMS-777607 and tivantinib, yielded stronger anti-tumor effects than INCB28060. Conclusion: RON and MET co-overexpression can be significant pathological characteristics in TNBC for poor prognosis. TKIs targeting RON and MET have stronger drug development potential for treating TNBC. [ABSTRACT FROM AUTHOR]

This paper provides an overview of current and future deployment of recyclable direct materials and sustainable materials through recycling of interconnect metals used in semiconductor assembly and packaging. Also, with the aim to study the key technical barriers, challenges of deployment and its reliability performance of impacts of sustainable materials used in semiconductor device packaging, this paper lays out the importance of noble metals and polymeric materials in terms of its materials sustainability for the next decade. This article briefly reviews key aspects of recycled materials reliability concerns, deployment of recycled gold (Au) wire, recycled copper (Cu), and other noble metals in semiconductor packaging and assembly. Frontend chip fabrication sustainability issues and their corresponding countermeasures are covered in this review article as well.

Up to 50% of head and neck squamous cell carcinoma (HNSCC) patients have lymph node (LN) metastasis, resulting in poor survival rate. Numerous studies have supported the notion that the alterations of gene expression and mechanical properties of cancer cells play an important role in cancer metastasis. However, which genes and how they regulate the biomechanical properties of HNSCC cells to promote LN metastasis remains elusive. In this study, we used an LN-metastatic mouse model in vivo to generate an LN-metastatic head and neck squamous cell carcinoma cell line and compared the differences in the biomolecular and biomechanical properties of LN-metastatic and non-metastatic cells. Our results showed that LN-metastatic cells had a higher level of Snail expression compared to non-LN-metastatic cells. The higher Snail expression promoted the cellular invasion capability in confined environments, mainly by increasing the longitudinal strain of the cell nuclei, which could be attributed to the stronger cell traction force and softer nuclear stiffness. These two biomechanical changes were correlated, respectively, to a larger amount of focal adhesion and less amount of nuclear lamins. Taken together, our works revealed not only the biomechanical profiles of LN-metastatic cells but also the corresponding biomolecular expressions to pinpoint the key process in LN metastasis.

The ZnO‐based Tamm plasmon‐polariton (TPP) ultraviolet laser is realized with the strong electric field confinement in the active layer. A coupling between TPPs and photons with a Rabi splitting of ≈30 meV is observed at room temperature. Furthermore, the TPP lasing at 373 nm is clearly observed by optical pumping. The corresponding lasing characteristics, such as threshold energy, linewidth, and angular dispersion curve are verified. These results form a basis for better understanding of the TPPs lasing mechanisms.

Ischiofemoral impingement syndrome is a neglected cause of posterior hip pain which is derived from narrowing of the space between the lateral aspect of the ischium and the medial aspect of the lesser trochanter. Its diagnosis is challenging and requires the combination of physical tests and imaging studies. In the present narrative review, we found that femoral anteversion predisposes patients to the narrowing of the ischiofemoral space and subsequent quadratus femoris muscle injury. Magnetic resonance imaging serves as the gold-standard diagnostic tool, which facilities the quantification of the ischiofemoral distance and the recognition of edema/fat infiltration/tearing of the quadratus femoris muscle. Ultrasound is useful for scrutinizing the integrity of deep gluteal muscles, and its capability to measure the ischiofemoral space is comparable to that of magnetic resonance. Various injection regimens can be applied to treat ischiofemoral impingement syndrome under ultrasound guidance and they appear to be safe and effective. Finally, more randomized controlled trials are needed to build solid bases of evidence on ultrasound-guided interventions in the management of ischiofemoral impingement syndrome.

Background: Postoperative atrial fibrillation (POAF) results in a longer hospital stay and excess mortality. However, whether POAF would increase stroke rate has been debated for years. When and how long should anticoagulation be used to prevent stroke are unknown. In the study, we planned to investigate the clinical demographics and long-term outcomes of POAF after cardiac surgery in a single-center cohort.Methods: The cohort study used a database from National Taiwan University Hospital, a single tertiary medical center in Taiwan, between 2007 and 2017, to identify patients with prior normal sinus rhythm developing POAF after cardiac surgery. Patients without POAF after cardiac surgery were used as controls. Propensity score matching with 1:1 ratio and Cox regression models were employed to estimate the risk of transient ischemic accident (TIA) or ischemic stroke.Results: From 2007 to 2017, a total of 8,374 patients received open-heart surgery, in which 1,585 patients with a history of AF were excluded. The overall incidence of TIA/ischemic stroke was 3.9% in a median 9.2-years of follow-up. After propensity matching, 1,965 matched paired subjects were included for analysis. Postoperative atrial fibrillation was associated with an increased risk of future AF [Hazard ratio (HR) 1.40, 95% confidence interval (95%CI) = 1.09–1.79, p = 0.008] and heart failure (HF) hospitalization (HR 1.58, 95%CI 1.23–2.04, p < 0.001); however, POAF did not significantly correlate with the risk of TIA/ischemic stroke (HR 1.17, 95%CI 0.85–1.60, p = 0.043). Kaplan-Meier analysis showed that POAF was a significant predictor for future AF, HF hospitalization, and overall mortality, but not for TIA/ischemic stroke.Conclusion: In the Asian population, POAF after cardiac surgery increased the risk of future AF, HF, and overall mortality, but was not associated with future TIA/ischemic stroke.

Abstract Background The use of oral progestin has been shown to effectively prevent luteining hormone (LH) surge during ovarian stimulation with daily human menopausal gonadotropin injections. This study was aimed to investigate the efficacy of long-acting follicle stimulating hormone (long-acting FSH; corifollitropin alfa, Elonva®) use in progestin-primed ovarian stimulation for normal and high responders undergoing IVF/ICSI. Methods This is a retrospective and proof-of-concept study. We developed an extremely patient-friendly protocol to be applied to forty-five normal or high responders, in which a single injection of corifollitropin alfa (Elonva®) was administered and medroxyprogesterone acetate (MPA) was taken orally every day from the day after Elonva injection to the day of trigger. Seven days after Elonva injection, folliculometry and hormone tests were performed, followed by short-acting daily FSH/LH injections, if needed, until the day before trigger. Duration of stimulation, number of injections and visits before trigger, incidence of premature LH surge, the number of oocytes retrieved, fertilization rate, cleavage rate, the rate of day 2 good embryos available, and cumulative ongoing pregnancy rate per retrieval were assessed. Results The average age of the population was 34.7 years. Duration of stimulation was 9.4 days in average. Before trigger, only 3.6 injection shots and 1.4 visits were needed on average. There was no case of premature LH surge. Number of oocytes retrieved was 13.7, fertilization rate was 79.04%, cleavage rate was 91.11%, and day 2 good embryo rate was 64.34%, in average respectively. There was no case of ovarian hyperstimulation syndrome. The cumulative ongoing pregnancy rate per oocyte retrieval achieved a satisfactory level as 53.1%. Conclusions Our protocol consisting of long-acting FSH injection and oral MPA preventing LH surge reduces the number of injections and visits to an extreme and achieves a satisfactory reproductive outcome, and, therefore, is a really patient-friendly and effective approach to ovarian stimulation.

BackgroundThe correlation between echocardiographic parameters and hemodynamics data in patients with heart failure with preserved ejection fraction (HFpEF) is unclear. It is important to find a non-invasive echocardiographic parameter for predicting exercise pulmonary capillary wedge pressure (PCWP).AimThis study sought to determine the correlation between echocardiographic parameters and hemodynamics data at rest and during exercise in HFpEF patients.Methods and ResultsThis study was a cross-sectional cohort exploratory analysis of baseline data from the ILO-HOPE trial. A total of 34 HFpEF patients were enrolled. The average age was 70 ± 12 years, and most (74%) were women. The patients underwent invasive cardiac catheterization and expired gas analysis at rest and during exercise. Echocardiography including tissue Doppler imaging was performed, and global longitudinal strain and other novel diastolic function indexes were analyzed at rest and during exercise. At rest, no significant correlation was noted between resting PCWP and echocardiographic parameters. However, a significant correlation was observed between post-exercise PCWP and stress E/e′ (septal, lateral, and mean) ratio (p = 0.003, 0.031, 0.012). Moreover, post-exercise ΔPCWP showed a good correlation with stress E/e′ (septal, lateral, and mean; all p ≤ 0.001) and global longitudinal strain (GLS) during exercise (p = 0.03). After multivariate regression analysis with adjustment for possible confounding factors including age and sex, there was still a significant correlation between post-exercise ΔPCWP and E/e′ (r = 0.62, p < 0.001 for E/e′mean).ConclusionOnly stress echocardiography derived tissue Doppler E/e′ ratio is closely correlated with abnormal exercise hemodynamics (PCWP and post-exercise ΔPCWP) in HFpEF. This echocardiographic marker is substantially more sensitive than other novel echocardiographic parameters during exercise, and may have significant diagnostic utility for ambulatory HFpEF patients with dyspnea.Clinical Trial Registrationhttps://www.clinicaltrials.gov, identifier NCT03620526.

Purpose: The purpose of this article is to present the first imaging experiments to demonstrate the functional equivalence between a conventional rotational gantry and a fixed-beam imaging geometry, and the feasibility of an iterative image-reconstruction technique under gravitational deformation. Methods and materials: Experiments were performed using an Elekta Axesse with Agility MLC and XVI, a custom-built rotating phantom stage, a Catphan QA phantom, and a porcine heart. For the imaging equivalence, a conventional cone beam computed tomography (CBCT) of the Catphan was acquired, as well as a set of 660 x-ray projections with a static gantry and rotating Catphan. Both datasets were reconstructed with the Feldkamp-Davis-Kress (FDK) algorithm, and the resultant volumetric images were compared using standard metrics. For imaging under gravitational deformation, a conventional CBCT of the Catphan and a set of 660 x-ray projections with a static gantry and rotating Catphan were also acquired with a porcine heart. The conventional CBCT was reconstructed using FDK. The projections that were acquired with the heart rotating were sorted into angular bins and reconstructed with prior image constrained compressed sensing using a deformation-blurred FDK prior. Deformation was quantified with B-spline transformation-based deformable image registration. Results: For imaging equivalence, the difference between the two Catphan images was consistent with Poisson noise. For imaging under gravitational deformation, the conventional CBCT porcine heart image (ground truth at 0 degrees) matched the static gantry, rotating heart reconstruction with a mean magnitude of

Uterine sarcoma is a very aggressive and highly lethal disease. Even after a comprehensive staging surgery or en block cytoreduction surgery followed by multimodality therapy (often chemotherapy and/or radiation therapy), many patients relapse or present with distant metastases, and finally die of diseases. The worst outcome of uterine sarcomas is partly because of their rarity, unknown etiology, and highly divergent genetic aberration. Uterine sarcomas are often classified into four distinct subtypes, including uterine leiomyosarcoma, low-grade uterine endometrial stromal sarcoma, high-grade uterine endometrial stromal sarcoma, and undifferentiated uterine sarcoma. Currently, evidence from tumor biology found that these tumors showed alternation and/or mutation of genomes and the intracellular signal pathway. In addition, some preclinical studies showed promising results for targeting receptor tyrosine kinase signaling, phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin pathway, various kinds of growth factor pathways, Wnt/beta-catenin signaling pathway, transforming growth factor β/bone morphogenetic protein signal pathway, aurora kinase A, MDM2 proto-oncogene, histone deacetylases, sex hormone receptors, certain types of oncoproteins, and/or loss of tumor suppressor genes. The current review is attempted to summarize the recurrent advance of targeted therapy for uterine sarcomas.

Uterine sarcomas account for 3–7% of all uterine cancers. Because of their rarity, unknown etiology, and highly divergent genetic aberration, there is a lack of consensus on risk factors for occurrence and predictive poor outcomes as well as optimal therapeutic choices. Tumor types according to the World Health Organization classification include leiomyosarcoma, endometrial stroma sarcoma, and undifferentiated sarcoma. Staging is done using the 2014 Federation International Gynecology and Obstetrics and 2010 American Joint Committee on Cancer tumor, lymph node, and metastases systems. Tumor grade can be classified based on the French Federation of Cancer Centers Sarcoma Group system or the Broder’s system that incorporates tumor differentiation, mitotic count, and tumor necrosis. This review is a series of articles discussing uterine sarcoma, and this is Part I, which focuses on one of the subtypes of uterine sarcomas—uterine leiomyosarcoma. The clinical characteristics, diagnosis, outcome, and recent advances are summarized in this article.

Endometrial stromal tumors are rare uterine tumors (

Our previous study showed a satisfactory reproductive outcome resulting from the patient-friendly ovarian stimulation protocol using long-acting follicle stimulation hormone (FSH) plus oral medroxyprogesterone acetate (MPA). The present retrospective study aims to compare the efficacy of the patient-friendly ovarian stimulation protocol with that of the antagonist protocol on normal and high responders aged between 24 and 39 years in a tertiary fertility center in Taiwan. To prevent premature luteinizing hormone (LH) surge, oral MPA was given to patients in group 1 (n = 57), whereas antagonist protocol was applied to group 2 (n = 53). Duration and dosage of stimulation, number of injections and visits before trigger, incidence of premature LH surge, number of oocytes retrieved, fertilization rate, cleavage rate, rate of good embryos available, incidence of ovarian hyperstimulation syndrome, cumulative clinical pregnancy rate and live birth rate per retrieval were compared between groups. We conclude that our patient-friendly ovarian stimulation protocol with MPA demonstrates satisfactory stimulation and reproductive outcomes that are comparable to those of an antagonist protocol.

Intrauterine adhesion (IUA), fibrosis, and scarring resulting from damage to the endometrium is a rare but serious clinical disease, contributing to a significant impairment of reproductive function. Uterine instrumentation, especially that of a hysteroscopic myomectomy, has become the main cause of IUA. Therefore, a prospective randomized controlled study to assess the effectiveness and short-term safety of the use of hyaluronic acid gels in the prevention of IUA after a hysteroscopic myomectomy and an evaluation of the characteristics of IUA observed at follow-up are presented here. A total of 70 patients were analyzed at the end of 16 March 2020. The results show that the incidence of IUA in women who underwent a hysteroscopic myomectomy is 21.4% (15/70), overall. Women treated with hyaluronic acid gels have a statistically significantly lower incidence of IUAs than non-treated women (12.8% vs. 39.1%, p = 0.012). In addition, women in the anti-adhesive gel treatment group had a dramatically reduced severity of IUA than women in the no-treatment group (p = 0.002). Further analysis shows that the International Federation of Gynecology and Obstetrics (FIGO) classification type and the use of anti-adhesive gels are independent factors associated with moderate and severe degrees of IUA formation. The results here highlight the significant therapeutic benefits of the application of hyaluronic acid gels in women undergoing a hysteroscopic myomectomy, especially for those patients with a uterine myoma classified as FIGO type 2. Since the risk of IUA after a hysteroscopic myomectomy is high, especially for patients who have not received prophylactic anti-adhesive gels, the application of hyaluronic acid gels as a prevention strategy is highly recommended. More studies are encouraged to confirm our observation.

Ankle/foot pain is a common complaint encountered in clinical practice. Currently, due to the complex anatomy, the diagnosis and management of the underlying musculoskeletal disorders are extremely challenging. Nowadays, high-resolution ultrasound has emerged as the first-line tool to evaluate musculoskeletal disorders. There have been several existing protocols describing the fundamental sonoanatomy of ankle/foot joints. However, there are certain anatomic structures (e.g., Lisfranc ligament complex or Baxter nerve) which are also clinically important. As they are rarely elaborated in the available literature, a comprehensive review is necessary. In this regard, the present article aims to brief the regional anatomy, illustrate the scanning techniques, and emphasize the clinical relevance of the ankle/foot region.

The Chinese version of the Continuity Assessment Record and Evaluation (CARE-C) item set was developed to facilitate the assessment of post-acute care (PAC) patients in Taiwan. Considering that the length of hospital stay (LOS) has a significant effect on the total healthcare cost, determining whether the CARE-C scores could predict the LOS of PAC patients is of great interest to the PAC providers.This prospective trial included PAC patients with stroke or central nervous system injuries. The demographic data and CARE-C scores were collected after admission and before discharge. A multivariable stepwise linear regression model was used to identify the predictors of the LOS using age, sex, tube placement status, CARE-C component scores at admission, and score differences between admission and discharge as independent variables.This study included 178 patients (66 women and 112 men), with a mean age of 61.9 ± 15.6 years. Indwelling urinary catheter placement status at admission (β = 0.241, p = 0.002) was a positive predictor of the LOS, whereas age (β = -0.189, p = 0.010), core transfer subscale score at admission (β = -0.176, p = 0.020), and difference in continence subscale score (β = -0.203, p = 0.008) were negative predictors of the LOS. The model explained 14% of the total variance.Indwelling urinary catheter placement status at admission, age, core transfer subscale score at admission, and difference in the CARE-C continence subscale score were identified as predictors of the LOS. The explanatory power of these predictors might be limited due to the regulations of Taiwan's National Health Insurance.

Objective: This paper reports the long-term follow-up (62–83 months) of women with unexplained subfertility secondary to severe adenomyosis treated with the combination of conservative surgery and gonadotropin releasing hormone agonist (GnRH agonist) therapy. Materials and Methods: A retrospective study included nine patients with a history of > 3 years of unexplained infertility who had extensive uterine adenomyosis. These nine couples were diagnosed with unexplained infertility after excluding other possible causes, such as the male factor, ovulation disorders, structural abnormality, and infections. All were essentially normal except for presumed uterine adenomyosis and elevated serum levels of CA125. All underwent a careful excision of the adenomyosis tissue using a microsurgical technique, and then a six-month course of GnRH agonist therapy. The outcome evaluations included serum level of CA125, degree of dysmenorrhea, and rate of spontaneous pregnancy. Results: Postoperative follow-up showed that the severity of dysmenorrhea was significantly improved. The improvement scale was positively correlated with a decline in the serum level of CA125. A postoperative serum CA125 decreased to less than 10.00 IU/mL predicted well the spontaneous pregnancy rate, especially during the therapy. In the end, only two women became pregnant and finally delivered viable babies in this study. Conclusions: Although the combination of careful conservative surgery and GnRH agonist therapy might provide some benefits in patients with unexplained infertility and presumed severe adenomyosis, two-thirds of the patients still failed to become pregnant. The postoperative serum level of CA125 could predict the future pregnancy rate.

Objective: This study analyzed whether continuous combined oral estradiol and norethisterone had any effect on the pulsatility index (PI) of the internal carotid and uterine arteries in Taiwanese early postmenopausal women. Materials and Methods: A group of 40 healthy postmenopausal women with no history of hormone therapy (HT) participated in this study and were randomly subdivided into two groups: HT treatment group (n = 20) and placebo group (n = 20). PI was evaluated with color Doppler ultrasound at the beginning of the study and after 4 months of HT (2 mg 17 β-estradiol + 1 mg norethisterone acetate) or placebo. Results: There was no significant change in the PI of the internal carotid and the uterine arteries after 4 months of HT. Conclusion: This HT regimen showed no significant negative impact on vascular resistance in Taiwanese early postmenopausal women. Results are compatible with the updated recommendations on HT stating that there is little cardiovascular risk when HT is initiated within a few years of the menopause.

BACKGROUND:The ageing process may lead to reductions in physical fitness, a known risk factor in the development of metabolic syndrome. The purpose of the current study was to evaluate cross-sectional and combined associations of metabolic syndrome with body composition and physical fitness in a community based geriatric population. METHODS:A total of 628 community-dwelling elders attending a geriatric health examination were enrolled in the study. The diagnosis of metabolic syndrome was based on the modified National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criterion with Asian cutoff of waist girth was adopted in this study. Body composition was obtained using bioimpedance analysis, and physical fitness was evaluated through the measurement of muscle strength (handgrip force), lower extremity muscle endurance (sit-to-stand test), flexibility (sit-and-reach test), and cardiorespiratory endurance (2-minute step test). Multivariable logistic regression and correlation analysis were performed to determine the association of metabolic syndrome with body composition and functionality variables. RESULTS:Metabolic syndrome was associated with increased skeletal muscle index (SMI) (odds ratio (OR), 1.61, 95% confidence interval (CI), 1.25-2.07) and decreased flexibility (OR, 0.97, 95% CI, 0.95-0.99) compared with those without metabolic syndrome. When body mass index was accounted for in the analysis, the association of SMI with metabolic syndrome was reduced. Waist circumference was positively correlated with SMI but negatively correlated with flexibility, whereas high density lipoprotein was positively correlated with flexibility but negatively correlated with SMI. CONCLUSION:Reduced flexibility was positively associated with metabolic syndrome independent of age, gender, body composition, and functionality measurements in a community based geriatric population. Significant associations between metabolic syndrome with muscle strength and cardiorespiratory fitness in the elderly were not observed. Furthermore, flexibility should be included in the complete evaluation for metabolic syndrome.

Concentric magnetic structures (ring and square) with domain wall (DW) pinning geometry are designed for biological manipulation. Magnetic beads collection was firstly demonstrated to analyse the local magnetic field generated by DWs and the effective regions to capture magnetic targets of size 1 μm. Primary mouse embryonic fibroblasts (MEFs) are magnetically labeled by internalizing poly (styrene sulfonic acid) stabilized magnetic nanoparticles (PSS-MNPs) and then are selectively trapped by head-to-tail DWs (HH DWs) or tail-to-tail DWs (TT DWs) to be arranged into linear shape or cross shape. The morphologies and the nuclear geometry of the cells growing on two kinds of concentric magnetic structures are shown to be distinctive. The intracellular magnetic forces generated by the local magnetic field of DWs are found to influence the behaviour of cells.

Measurements of the curvatures and warpages of a printed circuit board (PCB) during a thermal solder reflow process using strain gauges are proposed in this study. In the experiments, a shadow moiré is used for measuring the out-of-plane deformations (or warpage) of a bi-material plate and a PCB with dual in-line memory module (DIMM) sockets during solder reflow heating, while the finite element method (FEM) is used to analyze the thermally-induced deformation of the PCB specimen for ensuring the validity of the measurement. Conventional strain gauges are employed to measure the strains (albeit as in-plane strain data) in both specimens during the solder reflow process. The results indicate that the strain gauge-measured strain data from the top and bottom surfaces of both specimens during the solder reflow can be converted into curvature data with specific equations, and even into global out-of-plane deformations or warpages with a proposed simple beam model. Such results are also consistent with those from the shadow moiré and FEM. Therefore, it has been proved that the strain gauge measurement associated with the simple beam model can provide a method for the real-time monitoring of PCB deformations or warpages with different temperatures during the solder reflow process.

Developing methods that evaluate the cellular uptake of magnetic nanoparticles (MNPs) and nanotoxicity effects at single-cellular level are needed. In this study, magnetophoresis combining fluorescence based cytotoxicity assay was proposed to assess the viability and the single-cellular MNPs uptake simultaneously. Malignant cells (SKHep-1, HepG2, HeLa) were incubated with 10 nm anionic iron oxide nanoparticles. Prussian blue stain was performed to visualize the distribution of magnetic nanoparticles. MTT and fluorescence based assay analyzed the cytotoxicity effects of the bulk cell population and single cell, respectively. DAPI/PI stained was applied to evaluate death mechanism. The number of intracellular MNPs was found to be strongly correlated with the cell death. Significant differences between cellular MNP uptake in living and dead cells were observed. The method could be useful for future study of the nanotoxicity induced by MNPs.

Pathology of the long head biceps tendon (LHBT) is associated with rotator cuff tears but whether the LHBT texture changes following supraspinatus tendon full thickness tear (SSFT) can be detected at the extra-articular segment remains unknown. This cross-sectional study aimed to explore the morphological differences of the LHBT in shoulders with and without deficient rotator cuffs by using quantitative ultrasound.We selected 145 cases with SSFT and 145 age-and- gender-matched controls. The width, thickness, flattening ratio, cross-sectional area, and echogenicity ratio of the LHBT were measured and a general linear model was used to clarify the relationship between rotator cuff pathology and LHBT morphology. The receiver operating characteristic curves of each parameter were constructed for SSFT discrimination and the maximal Youden indexes were used to define the best cut-off points.We found increased thickness and cross-sectional area but decreased flattening ratio in shoulders with SSFT, and no between-group differences in the width and echogenicity ratio. The LHBT appearance was modified by biceps peritendinous effusion and medial subluxation, but not by the size of SSFT. The flattening ratio was the best discriminator for SSFT with an area under curve of 0.81 (95% confidence interval, 0.76-0.86). The cut-off values to differentiate between the non-tear and tear groups were 2.00 mm of the thickness, 1.73 of the flattening ratio and 10.53 mm(2) of the cross-sectional area.Quantitative ultrasound facilitated the detection of the LHBT morphological changes following SSFT and demonstrated its potential utility in discriminating rotator cuff deficiency.

BACKGROUND: Photoaging is cumulative damage to skin, caused by chronic, repeated solar radiation exposure. Its molecular mechanisms are poorly understood at the level of global gene expression. OBJECTIVE: This study set out to uncover genes and functional modules involved in photoaging at the level of transcription, with the use of skin samples from Chinese women. METHODS: Using the Illumina microarray platform, we compared the genome-wide expression profiles of 21 pairs of sun-exposed pre-auricular and sun-protected post-auricular skin samples from northern Chinese women. RESULTS: With microarray analysis, 1,621 significantly regulated genes due to photoaging were identified from skin samples. These genes were subjected to functional enrichment analyses with both the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation databases. As revealed by the functional analyses, the up-regulated functional modules in sun-exposed pre-auricular skin were related to various cellular activities in regulation of the skin homeostasis (e.g., the KEGG pathways TGF-beta signaling pathway and ECM-receptor interaction), whereas the down-regulated functional modules were mostly metabolic-related. Additionally, five selected genes (HOXA5, LEPR, CLDN5, LAMC3, and CGA) identified as differentially-expressed were further confirmed by quantitative real-time PCR (Q-RT-PCR). CONCLUSION: Our findings suggest that disruption of skin homeostasis and down-regulation of skin metabolism may play important roles in the process of photoaging.

BACKGROUND: Various pharmacologic and non-pharmacologic approaches have been applied to reduce sublesional bone loss after spinal cord injury (SCI), and the results are inconsistent across the studies. The objective of this meta-analysis was to investigate whether the two most-studied interventions, bisphosphonate analogues and functional electrical stimulation (FES), could effectively decrease bone mineral density (BMD) attenuation and/or restore lost BMD in the SCI population. METHODS: Randomized controlled trials, quasi-experimental studies, and prospective follow-up studies employing bisphosphonates or FES to treat post-SCI osteoporosis were identified in PubMed and Scopus. The primary outcome was the percentage of BMD change from baseline measured by dual-energy X-ray absorptiometry (DEXA) or computed tomography (CT). Data were extracted from four points: the 3rd, 6th, 12th, and 18th month after intervention. RESULTS: A total of 19 studies were included in the analysis and involved 364 patients and 14 healthy individuals. Acute SCI participants treated with bisphosphonate therapy demonstrated a trend toward less bone loss than participants who received placebos or usual care. A significant difference in BMD decline was noted between both groups at the 3rd and 12th month post-medication. The subgroup analysis failed to show the superiority of intravenous bisphosphonate over oral administration. Regarding FES training, chronic SCI patients had 5.96% (95% CI, 2.08% to 9.84%), 7.21% (95%CI, 1.79% to 12.62%), and 9.56% (95% CI, 2.86% to 16.26%) increases in BMD at the 3rd, 6th, and 12th months post-treatment, respectively. The studies employing FES ≥ 5 days per week were likely to have better effectiveness than studies using FES ≤ 3 days per week. CONCLUSIONS: Our meta-analysis indicated bisphosphonate administration early following SCI effectively attenuated sublesional bone loss. FES intervention for chronic SCI patients could significantly increase sublesional BMD near the site of maximal mechanical loading.